Abstract
Extracellular senile plaques and intracellular neurofibrillary tangles are the neuropathological findings of the Alzheimer’s disease (AD). Based on the amyloid cascade hypothesis, the main component of senile plaques, the amyloid-beta (Aβ) peptide, and its derivative called amyloid precursor protein (APP) both have been found to place their central roles in AD development for years. However, the recent therapeutics have yet to reverse or halt this disease. Previous evidence demonstrates that the accumulation of Aβ peptides and APP can exert neurotoxicity and ultimately neuronal cell death. Hence, we discuss the mechanisms of excessive production of Aβ peptides and APP serving as pathophysiologic stimuli for the initiation of various cell signalling pathways including apoptosis, necrosis, necroptosis and autophagy which lead to neuronal cell death. Conversely, the activation of such pathways could also result in the abnormal generation of APP and Aβ peptides. An elucidation of actions of APP and its metabolite, Aβ, could be vital in suggesting novel therapeutic opportunities.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- AD:
-
Alzheimer’s disease
- APP :
-
Amyloid precursor protein
- PSEN1/2 :
-
Presenilin 1/2
- Aβ :
-
Amyloid-β
- KPI :
-
Kunitz protease inhibitor
- BACE1 :
-
β-Secretase
- sAPPα :
-
Soluble ectodomain APP
- AICD :
-
APP intracellular domain
- AChE :
-
Acetylcholinesterase
- TNF :
-
Tumour necrosis factor
- FasR :
-
First apoptosis signal receptor
- FADD :
-
Fas-associated death domain
- DED :
-
Death effector domain
- DISC :
-
Death-inducing signalling complex
- DR6 :
-
Death receptor 6
- N-APP :
-
N-Terminus of β-amyloid precursor protein
- TRADD :
-
TNF receptor-associated death domain
- RIP :
-
Receptor-interacting protein
- TRAF2 :
-
TNF receptor-associated factor 2
- NF-kB :
-
Nuclear factor-kappa B
- JAK :
-
Janus Kinase
- MOMP :
-
Mitochondrial outer membrane permeabilization
- MPTP :
-
Mitochondrial permeability transition pore
- VDAC :
-
Voltage-dependent anion channel
- UPR :
-
Unfolded protein response
- PERK :
-
Pancreatic ER Kinase
- ATF :
-
Activating transcription factor
- IRE1 :
-
Inositol-requiring enzyme 1
- GRP78 :
-
Glucose-related protein 78
- eIF2α :
-
Eukaryotic initiation factor 2α
- XBP1 :
-
X box-binding protein 1
- MAPK :
-
Mitogen-activated protein Kinase
- PS1 :
-
Presenilin 1
- MVBs :
-
Multivesicular bodies
- DRMs :
-
Detergent-resistant membranes
- MLKL :
-
Mixed lineage Kinase domain-like protein
- RHIM :
-
RIP homotypic interaction motif
- h-APP :
-
Full-length APP
- 24S-OHC :
-
24(S)-Hydroxycholesterol
- ACAT1 :
-
Acyl-CoA: Cholesterol Acyltransferase 1
- ROS :
-
Reactive oxygen species
- RSL3 :
-
RAS-selective lethal 3
- GSH :
-
Glutathione
- GPX4 :
-
Glutathione peroxidase 4
- LOXs :
-
Lipoxygenases
- AIF :
-
Apoptosis-inducing factor
- NOD :
-
Nucleotide-binding and oligomerization
- NLRP :
-
NOD-, Leucine-rich repeat and Pyrin domain-containing protein
- Atg :
-
Autophagy-related
- LC3 :
-
Light Chain 3
- ULK1 :
-
Unc-51 like autophagy activating Kinase 1
- PIK3C3 :
-
Class 3 phosphoinositide-3-Kinase
- UVRAG :
-
UV irradiation resistance-associated gene
- AVs :
-
Autophagic vacuoles
- TRPML1 :
-
Transient receptor potential mucolipin-1
- ALR :
-
Autophagic lysosome reformation
- PPARγ/AMPK/mTOR :
-
Peroxisome proliferator-activated receptor γ/AMP activated protein Kinase/Mammalian target of Rapamycin
- PINK1 :
-
Phosphatase and Tensin Homolog-induced Putative Kinase 1
- PK :
-
Parkin
- OPTN :
-
Optineurin
- NDP52 :
-
Nuclear dot protein 52
- v-ATPase :
-
Vacuolar ATPase
- βCTF :
-
β-C-terminal fragment
- αCTF :
-
α-C-terminal fragment
- APLP1 :
-
Amyloid precursor-like protein 1
- JNK :
-
c-Jun N-terminal Kinase
References
Alzheimer A, Stelzmann RA, Schnitzlein HN, Murtagh FR (1995) An english translation of Alzheimer’s 1907 paper, “Uber eine eigenartige Erkankung der Hirnrinde”. Clin Anat 8:429–431. https://doi.org/10.1002/ca.980080612
Anagnostaras SG, Murphy GG, Hamilton SE, Mitchell SL, Rahnama NP, Nathanson NM, Silva AJ (2003) Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice. Nat Neurosci 6:51–58. https://doi.org/10.1038/nn992
Antharam V, Collingwood JF, Bullivant JP, Davidson MR, Chandra S, Mikhaylova A, Finnegan ME, Batich C, Forder JR, Dobson J (2012) High field magnetic resonance microscopy of the human hippocampus in Alzheimer’s disease: quantitative imaging and correlation with iron. Neuroimage 59:1249–1260. https://doi.org/10.1016/j.neuroimage.2011.08.019
Artal-Sanz M, Tavernarakis N (2005) Proteolytic mechanisms in necrotic cell death and neurodegeneration. FEBS Lett 579:3287–3296. https://doi.org/10.1016/j.febslet.2005.03.052
Asada R, Kanemoto S, Kondo S, Saito A, Imaizumi K (2011) The signalling from endoplasmic reticulum-resident bZIP transcription factors involved in diverse cellular physiology. J Biochem 149:507–518. https://doi.org/10.1093/jb/mvr041
Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281:1305–1308. https://doi.org/10.1126/science.281.5381.1305
Bae M, Patel N, Xu H, Lee M, Tominaga-Yamanaka K, Nath A, Geiger J, Gorospe M, Mattson MP, Haughey NJ (2014) Activation of TRPML1 clears intraneuronal Aβ in preclinical models of HIV infection. J Neurosci 34:11485–11503. https://doi.org/10.1523/JNEUROSCI.0210-14.2014
Baranello RJ, Bharani KL, Padmaraju V, Chopra N, Lahiri DK, Greig NH, Pappolla MA, Sambamurti K (2015) Amyloid-beta protein clearance and degradation (ABCD) pathways and their role in Alzheimer’s disease. Curr Alzheimer Res 12:32–46. https://doi.org/10.2174/1567205012666141218140953
Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC, Dominantly Inherited Alzheimer Network (2012) Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 367:795–804. https://doi.org/10.1056/NEJMoa1202753
Báthori G, Szabó I, Schmehl I, Tombola F, Messina A, De Pinto V, Zoratti M (1998) Novel aspects of the electrophysiology of mitochondrial porin. Biochem Biophys Res Commun 243:258–263. https://doi.org/10.1006/bbrc.1997.7926
B'chir W, Maurin AC, Carraro V, Averous J, Jousse C, Muranishi Y, Parry L, Stepien G, Fafournoux P, Bruhat A (2013) The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res 41:7683–7699. https://doi.org/10.1093/nar/gkt563
Beach A, Zhang HG, Ratajczak MZ, Kakar SS (2014) Exosomes: an overview of biogenesis, composition and role in ovarian cancer. J Ovarian Res 7:14. https://doi.org/10.1186/1757-2215-7-14
Behl C, Moosmann B (2002) Antioxidant neuroprotection in Alzheimer’s disease as preventive and therapeutic approach. Free Radic Biol Med 33:182–191. https://doi.org/10.1016/S0891-5849(02)00883-3
Bendiske J, Bahr BA (2003) Lysosomal activation is a compensatory response against protein accumulation and associated synaptopathogenesis – an approach for slowing Alzheimer disease? J Neuropathol Exp Neurol 62:451–463. https://doi.org/10.1093/jnen/62.5.451
Björkhem I, Lütjohann D, Breuer O, Sakinis A, Wennmalm A (1997) Importance of a novel oxidative mechanism for elimination of brain cholesterol. Turnover of cholesterol and 24(S)-hydroxycholesterol in rat brain as measured with 18O2 techniques in vivo and in vitro. J Biol Chem 272:30178–30184. https://doi.org/10.1074/jbc.272.48.30178
Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer’s disease. Lancet 368:387–403. https://doi.org/10.1016/S0140-6736(06)69113-7
Bordji K, Becerril-Ortega J, Nicole O, Buisson A (2010) Activation of extrasynaptic, but not synaptic, NMDA receptors modifies amyloid precursor protein expression pattern and increases amyloid-β production. J Neurosci 30:15927–15924. https://doi.org/10.1523/JNEUROSCI.3021-10.2010
Bozyczko-Coyne D, O'Kane TM, Wu ZL, Dobrzanski P, Murthy S, Vaught JL, Scott RW (2001) CEP-1347/KT-7515, an inhibitor of SAPK/JNK pathway activation, promotes survival and blocks multiple events associated with Abeta-induced cortical neuron apoptosis. J Neurochem 77:849–863. https://doi.org/10.1046/j.1471-4159.2001.00294.x
Brakebusch C, Nophar Y, Kemper O, Engelmann H, Wallach D (1992) Cytoplasmic truncation of the p55 tumour necrosis factor (TNF) receptor abolishes signalling, but not induced shedding of the receptor. EMBO J 11:943–950
Brigelius-Flohé R, Maiorino M (2013) Glutathione peroxidases. Biochim Biophys Acta 1830:3289–3303. https://doi.org/10.1016/j.bbagen.2009.03.006
Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 3:186–191. https://doi.org/10.1016/j.jalz.2007.04.381
Buée L, Bussière T, Buée-Scherrer V, Delacourte A, Hof PR (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 33:95–130. https://doi.org/10.1016/S0165-0173(00)00019-9
Bustos V, Pulina MV, Kelahmetoglu Y, Sinha SC, Gorelick FS, Flajolet M, Greengard P (2017) Bidirectional regulation of Aβ levels by presenilin 1. Proc Natl Acad Sci U S A 114:7142–7147. https://doi.org/10.1073/PNAS.1705235114
Butterfield DA (2002) Amyloid beta-peptide (1–42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer’s disease brain. A review. Free Radic Res 36:1307–1313. https://doi.org/10.1080/1071576021000049890
Caccamo A, Oddo S, Billings LM, Green KN, Martinez-Coria H, Fisher A, LaFerla FM (2006) M1 receptors play a central role in modulating AD-like pathology in transgenic mice. Neuron 48:671–682. https://doi.org/10.1016/j.neuron.2006.01.020
Cai Z, Jitkaew S, Zhao J, Chiang HC, Choksi S, Liu J, Ward Y, Wu LG, Liu ZG (2014) Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat Cell Biol 16:55–65. https://doi.org/10.1038/ncb2883
Caillé I, Allinquant B, Dupont E, Bouillot C, Langer A, Müller U, Prochiantz A (2004) Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone. Development 131:2173–2181. https://doi.org/10.1242/dev.01103
Caldwell JH, Klevanski M, Saar M, Müller UC (2013) Roles of the amyloid precursor protein family in the peripheral nervous system. Mech Dev 130:433–446. https://doi.org/10.1016/j.mod.2012.11.001
Canevari L, Abramov AY, Duchen MR (2004) Toxicity of amyloid β peptide: tales of calcium, mitochondria, and oxidative stress. Neurochem Res 29:637–650. https://doi.org/10.1023/B:NERE.0000014834.06405.af
Caporaso GL, Takei K, Gandy SE, Matteoli M, Mundigl O, Greengard P, De Camilli P (1994) Morphologic and biochemical analysis of the intracellular trafficking of the Alzheimer beta/A4 amyloid precursor protein. J Neurosci 14:3122–3138. https://doi.org/10.1523/JNEUROSCI.14-05-03122.1994
Certo M, Del Gaizo Moore V, Nishino M, Wei G, Korsmeyer S, Armstrong SA, Letai A (2006) Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell 9:351–365. https://doi.org/10.1016/j.ccr.2006.03.027
Chang KA, Kim HS, Ha TY, Ha JW, Shin KY, Jeong YH, Lee JP, Park CH, Kim S, Baik TK, Suh YH (2006) Phosphorylation of amyloid precursor protein (APP) at Thr668 regulates the nuclear translocation of the APP intracellular domain and induces neurodegeneration. Mol Cell Biol 26:4327–4338. https://doi.org/10.1128/MCB.02393-05
Chang TY, Li BL, Chang CC, Urano Y (2009) Acyl-coenzyme A: cholesterol acyltransferases. Am J Physiol Endocrinol Metab 297:E1–E9. https://doi.org/10.1152/ajpendo.90926.2008
Chasseigneaux S, Allinquant B (2012) Functions of Aβ, sAPPα and sAPPβ : similarities and differences. J Neurochem 120(Suppl 1):99–108. https://doi.org/10.1111/j.1471-4159.2011.07584.x
Cheng EH, Sheiko TV, Fisher JK, Craigen WJ, Korsmeyer SJ (2003) VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science 301:513–517. https://doi.org/10.1126/science.1083995
Cheng X, Shen D, Samie M, Xu H (2010) Mucolipins: intracellular TRPML1–3 channels. FEBS Lett 584:2013–2021. https://doi.org/10.1016/j.febslet.2009.12.056
Chia KY, Ng KY, Koh RY, Chye SM (2018) Single-chain Fv antibodies for targeting neurodegenerative diseases. CNS Neurol Disord Drug Targets 17:671–679. https://doi.org/10.2174/1871527317666180315161626
Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM (1995) FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosis. Cell 81:505–512. https://doi.org/10.1016/0092-8674(95)90071-3
Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137:1112–1123. https://doi.org/10.1016/j.cell.2009.05.037
Chong FP, Ng KY, Koh RY, Chye SM (2018) Tau proteins and tauopathies in Alzheimer’s disease. Cell Mol Neurobiol 38:965–980. https://doi.org/10.1007/s10571-017-0574-1
Clarke PG (1990) Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol (Berl) 181:195–213. https://doi.org/10.1007/BF00174615
Colacurcio DJ, Nixon RA (2016) Disorders of lysosomal acidification – the emerging role of v-ATPase in aging and neurodegenerative disease. Ageing Res Rev 32:75–88. https://doi.org/10.1016/j.arr.2016.05.004
Coman H, Nemeş B (2017) New therapeutic targets in Alzheimer’s disease. Int J Gerontol 11:2–6. https://doi.org/10.1016/j.ijge.2016.07.003
Conde JR, Streit WJ (2006) Microglia in the aging brain. J Neuropath Exp Neur 65:199–203. https://doi.org/10.1097/01.jnen.0000202887.22082.63
Cory S, Adams JM (2002) The BCL2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656. https://doi.org/10.1038/nrc883
Curcio-Morelli C, Charles FA, Micsenyi MC, Cao Y, Venugopal B, Browning MF, Dobrenis K, Cotman SL, Walkley SU, Slaugenhaupt SA (2010) Macroautophagy is defective in mucolipin-1-deficient mouse neurons. Neurobiol Dis 40:370–377. https://doi.org/10.1016/j.nbd.2010.06.010
Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219. https://doi.org/10.1016/S0092-8674(04)00046-7
De Strooper B (2010) Proteases and proteolysis in alzheimer disease: a multifactorial view on the disease process. Physiol Rev 90:465–494. https://doi.org/10.1152/physrev.00023.2009
Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, Cuny GD, Mitchison TJ, Moskowitz MA, Yuan J (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 1:112–119. https://doi.org/10.1038/nchembio711
Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4:313–321. https://doi.org/10.1038/nchembio.83
Del Gaizo Moore V, Brown JR, Certo M, Love TM, Novina CD, Letai A (2007) Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J Clin Invest 117:112–121. https://doi.org/10.1172/JCI28281
Delrieu J, Ousset PJ, Caillaud C, Vellas B (2012a) 'Clinical trials in Alzheimer’s disease': immunotherapy approaches. J Neurochem 120:186–193. https://doi.org/10.1111/j.1471-4159.2011.07458.x
Delrieu J, Ousset PJ, Vellas B (2012b) Gantenerumab for the treatment of Alzheimer’s disease. Expert Opin Biol Ther 12:1077–1086. https://doi.org/10.1517/14712598.2012.688022
Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B 3rd, Stockwell BR (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060–1072. https://doi.org/10.1016/j.cell.2012.03.042
Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I, Irmler M, Beckers J, Aichler M, Walch A, Prokisch H, Trümbach D, Mao G, Qu F, Bayir H, Füllekrug J, Scheel CH, Wurst W, Schick JA, Kagan VE, Angeli JP, Conrad M (2017) ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol 13:91–98. https://doi.org/10.1038/nchembio.2239
Dondelinger Y, Declercq W, Montessuit S, Roelandt R, Goncalves A, Bruggeman I, Hulpiau P, Weber K, Sehon CA, Marquis RW, Bertin J, Gough PJ, Savvides S, Martinou JC, Bertrand MJ, Vandenabeele P (2014) MLKL compromises plasma membrane integrity by binding to phosphatidylinositol phosphates. Cell Rep 7:971–981. https://doi.org/10.1016/j.celrep.2014.04.026
Du F, Yu Q, Yan S, Hu G, Lue LF, Walker DG, Wu L, Yan SF, Tieu K, Yan SS (2017) PINK1 signalling rescues amyloid pathology and mitochondrial dysfunction in Alzheimer’s disease. Brain 140:3233–3251. https://doi.org/10.1093/brain/awx258
Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516. https://doi.org/10.1080/01926230701320337
Engel PA (2014) Does metabolic failure at the synapse cause Alzheimer’s disease? Med Hypotheses 83:802–808. https://doi.org/10.1016/j.mehy.2014.10.013
Eskelinen EL (2005) Maturation of autophagic vacuoles in mammalian cells. Autophagy 1:1–10. https://doi.org/10.4161/auto.1.1.1270
Farrall AJ, Wardlaw JM (2009) Blood-brain barrier: ageing and microvascular disease – systematic review and meta-analysis. Neurobiol Aging 30:337–352. https://doi.org/10.1016/j.neurobiolaging.2007.07.015
Feng H, Stockwell BR (2018) Unsolved mysteries: how does lipid peroxidation cause ferroptosis? PLoS Biol 16:e2006203. https://doi.org/10.1371/journal.pbio.2006203
Feng T, Tammineni P, Agrawal C, Jeong YY, Cai Q (2017) Autophagy-mediated regulation of BACE1 protein trafficking and degradation. J Biol Chem 292:1679–1690. https://doi.org/10.1074/jbc.M116.766584
Ferreiro E, Resende R, Costa R, Oliveira CR, Pereira CM (2006) An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity. Neurobiol Dis 23:669–678. https://doi.org/10.1016/j.nbd.2006.05.011
Ferreiro E, Oliveira CR, Pereira CM (2008) The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway. Neurobiol Dis 30:331–342. https://doi.org/10.1016/j.nbd.2008.02.003
Fisher A, Pittel Z, Haring R, Bar-Ner N, Kliger-Spatz M, Natan N, Egozi I, Sonego H, Marcovitch I, Brandeis R (2003) M1 muscarinic agonists can modulate some of the hallmarks in Alzheimer’s disease: implications in future therapy. J Mol Neurosci 20:349–356. https://doi.org/10.1385/JMN:20:3:349
Freeman LC, Ting JPY (2016) The pathogenic role of the inflammasome in neurodegenerative diseases. J Neurochem 136:29–38. https://doi.org/10.1111/jnc.13217
Fukumoto H, Rosene DL, Moss MB, Raju S, Hyman BT, Irizarry MC (2004) Beta-secretase activity increases with aging in human, monkey, and mouse brain. Am J Pathol 164:719–725. https://doi.org/10.1016/S0002-9440(10)63159-8
Fulda S, Gorman AM, Hori O, Samali A (2010) Cellular stress responses: cell survival and cell death. Int J Cell Biol 2010:214074. https://doi.org/10.1155/2010/214074
Furukawa K, Sopher BL, Rydel RE, Begley JG, Pham DG, Martin GM, Fox M, Mattson MP (1996) Increased activity-regulating and neuroprotective efficacy of α-secretase-derived secreted amyloid precursor protein conferred by a C-terminal heparin-binding domain. J Neurochem 67:1882–1896. https://doi.org/10.1046/j.1471-4159.1996.67051882.x
Furuya N, Yu J, Byfield M, Pattingre S, Levine B (2005) The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy 1:46–52. https://doi.org/10.4161/auto.1.1.1542
Galehdar Z, Swan P, Fuerth B, Callaghan SM, Park DS, Cregan SP (2010) Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA. J Neurosci 30:16938–16948. https://doi.org/10.1523/JNEUROSCI.1598-10.2010
Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, Gottlieb E, Green DR, Hengartner MO, Kepp O, Knight RA, Kumar S, Lipton SA, Lu X, Madeo F, Malorni W, Mehlen P, Nuñez G, Peter ME, Piacentini M, Rubinsztein DC, Shi Y, Simon HU, Vandenabeele P, White E, Yuan J, Zhivotovsky B, Melino G, Kroemer G (2012) Molecular definitions of cell death subroutines: recommendations of the nomenclature committee on cell death 2012. Cell Death Differ 19:107–120. https://doi.org/10.1038/cdd.2011.96
Galonek HL, Hardwick JM (2006) Upgrading the BCL-2 network. Nat Cell Biol 8:1317–1319. https://doi.org/10.1038/ncb1206-1317
Gamba P, Guglielmotto M, Testa G, Monteleone D, Zerbinati C, Gargiulo S, Biasi F, Iuliano L, Giaccone G, Mauro A, Poli G, Tamagno E, Leonarduzzi G (2014) Up-regulation of β-amyloidogenesis in neuron-like human cells by both 24- and 27-hydroxycholesterol: protective effect of N-acetyl-cysteine. Aging Cell 13:561–572. https://doi.org/10.1111/acel.12206
Gandhi S, Wood-Kaczmar A, Yao Z, Plun-Favreau H, Deas E, Klupsch K, Downward J, Latchman DS, Tabrizi SJ, Wood NW, Duchen MR, Abramov AY (2009) PINK1-associated Parkinson’s disease is caused by neuronal vulnerability to calcium-induced cell death. Mol Cell 33:627–638. https://doi.org/10.1016/j.molcel.2009.02.013
Gendron TF, Petrucelli L (2009) The role of tau in neurodegeneration. Mol Neurodegener 4:13. https://doi.org/10.1186/1750-1326-4-13
Gerakis Y, Hetz C (2018) Emerging roles of ER stress in the etiology and pathogenesis of Alzheimer’s disease. FEBS J 285:995–1011. https://doi.org/10.1111/febs.14332
Gervais FG, Xu D, Robertson GS, Vaillancourt JP, Zhu Y, Huang J, LeBlanc A, Smith D, Rigby M, Shearman MS, Clarke EE, Zheng H, Van Der Ploeg LH, Ruffolo SC, Thornberry NA, Xanthoudakis S, Zamboni RJ, Roy S, Nicholson DW (1999) Involvement of caspases in proteolytic cleavage of Alzheimer’s amyloid-β precursor protein and amyloidogenic Aβ peptide formation. Cell 97:395–406. https://doi.org/10.1016/S0092-8674(00)80748-5
Geylis V, Steinitz M (2006) Immunotherapy of Alzheimer’s disease (AD): from murine models to anti-amyloid beta (Aβ) human monoclonal antibodies. Autoimmun Rev 5:33–39. https://doi.org/10.1016/j.autrev.2005.06.007
Ghosh AK, Tang J (2015) Prospects of β-secretase inhibitors for the treatment of Alzheimer’s disease. ChemMedChem 10:1463–1466. https://doi.org/10.1002/cmdc.201500216
Ghosh AK, Gemma S, Tang J (2008) Beta-secretase as a therapeutic target for Alzheimer’s disease. Neurotherapeutics 5:399–408. https://doi.org/10.1016/j.nurt.2008.05.007
Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, Mant R, Newton P, Rooke K, Roques P, Talbot C, Pericak-Vance M, Roses A, Williamson R, Rossor M, Owen M, Hardy J (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349:704–706. https://doi.org/10.1038/349704a0
Gonzalvez F, Ashkenazi A (2010) New insights into apoptosis signaling by Apo2L/TRAIL. Oncogene 29:4752–4765. https://doi.org/10.1038/onc.2010.221
Gorman AM (2008) Neuronal cell death in neurodegenerative diseases: recurring themes around protein handling. J Cell Mol Med 12:2263–2280. https://doi.org/10.1111/j.1582-4934.2008.00402.x
Gouras GK, Tsai J, Naslund J, Vincent B, Edgar M, Checler F, Greenfield JP, Haroutunian V, Buxbaum JD, Xu H, Greengard P, Relkin NR (2000) Intraneuronal Aβ42 accumulation in human brain. Am J Pathol 156:15–20. https://doi.org/10.1016/S0002-9440(10)64700-1
Gralle M, Botelho MG, Wouters FS (2009) Neuroprotective secreted amyloid precursor protein acts by disrupting amyloid precursor protein dimers. J Biol Chem 284:15016–15025. https://doi.org/10.1074/jbc.M808755200
Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626–629. https://doi.org/10.1126/science.1099320
Greenfield JP, Tsai J, Gouras GK, Hai B, Thinakaran G, Checler F, Sisodia SS, Greengard P, Xu H (1999) Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides. Proc Natl Acad Sci U S A 96:742–747. https://doi.org/10.1073/pnas.96.2.742
Grill JD, Cummings JL (2010) Current therapeutic targets for the treatment of Alzheimer’s disease. Expert Rev Neurother 10:711–728. https://doi.org/10.1586/ern.10.29
Guerreiro R, Bras J (2015) The age factor in Alzheimer’s disease. Genome Med 7:106. https://doi.org/10.1186/s13073-015-0232-5
Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ, Golenbock DT (2008) The NALP3 inflammasome is involved in the innate immune response to amyloid-β. Nat Immunol 9:857–865. https://doi.org/10.1038/ni.1636
Hanson B (2016) Necroptosis: a new way of dying? Cancer Biol Ther 17:899–910. https://doi.org/10.1080/15384047.2016.1210732
Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, Ron D (2000) Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell 6:1099–1108. https://doi.org/10.1016/S1097-2765(00)00108-8
Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184–185. https://doi.org/10.1126/science.1566067
Hartmann T, Bieger SC, Brühl B, Tienari PJ, Ida N, Allsop D, Roberts GW, Masters CL, Dotti CG, Unsicker K, Beyreuther K (1997) Distinct sites of intracellular production for Alzheimer’s disease Aβ40/42 amyloid peptides. Nat Med 3:1016–1020. https://doi.org/10.1038/nm0997-1016
Hashimoto S, Saido TC (2018) Critical review: involvement of endoplasmic reticulum stress in the aetiology of Alzheimer’s disease. Open Biol 8:180024. https://doi.org/10.1098/rsob.180024
He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43:67–93. https://doi.org/10.1146/annurev-genet-102808-114910
He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-α. Cell 137:1100–1111. https://doi.org/10.1016/j.cell.2009.05.021
Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, Gelpi E, Halle A, Korte M, Latz E, Golenbock DT (2013) NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature 493:674–678. https://doi.org/10.1038/nature11729
Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776. https://doi.org/10.1038/35037710
Henke N, Albrecht P, Bouchachia I, Ryazantseva M, Knoll K, Lewerenz J, Kaznacheyeva E, Maher P, Methner A (2013) The plasma membrane channel ORAI1 mediates detrimental calcium influx caused by endogenous oxidative stress. Cell Death Dis 4:e470. https://doi.org/10.1038/cddis.2012.216
Heredia L, Lin R, Vigo FS, Kedikian G, Busciglio J, Lorenzo A (2004) Deposition of amyloid fibrils promotes cell-surface accumulation of amyloid β precursor protein. Neurobiol Dis 16:617–629. https://doi.org/10.1016/j.nbd.2004.04.015
Ho L, Ki F, Younkin SG (1996) The alternatively spliced Kunitz protease inhibitor domain alters amyloid beta protein precursor processing and amyloid beta protein production in cultured cells. J Biol Chem 271:30929–30934. https://doi.org/10.1074/JBC.271.48.30929
Hornung JP, Koppel H, Clarke PG (1989) Endocytosis and autophagy in dying neurons: an ultrastructural study in chick embryos. J Comp Neurol 283:425–437. https://doi.org/10.1002/cne.902830310
Hsu H, Xiong J, Goeddel DV (1995) The TNF receptor 1-associated protein TRADD signals cell death and NF-κB activation. Cell 81:495–504. https://doi.org/10.1016/0092-8674(95)90070-5
Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV (1996a) TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity 4:387–396. https://doi.org/10.1016/S1074-7613(00)80252-6
Hsu H, Shu HB, Pan MG, Goeddel DV (1996b) TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84:299–308. https://doi.org/10.1016/S0092-8674(00)80984-8
Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, Scarpa RC, Saunders AJ, Lim J, Moir RD, Glabe C, Bowden EF, Masters CL, Fairlie DP, Tanzi RE, Bush AI (1999) Cu(II) potentiation of Alzheimer aβ neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem 274:37111–37116. https://doi.org/10.1074/jbc.274.52.37111
Huang WJ, Zhang X, Chen WW (2016) Role of oxidative stress in Alzheimer’s disease. Biomed Rep 4:519–522. https://doi.org/10.3892/br.2016.630
Hung SY, Huang WP, Liou HC, Fu WM (2009) Autophagy protects neuron from Aβ-induced cytotoxicity. Autophagy 5:502–510. https://doi.org/10.4161/auto.5.4.8096
Hyman BT, Tanzi RE, Marzloff K, Barbour R, Schenk D (1992) Kunitz protease inhibitor-containing amyloid β protein precursor immunoreactivity in Alzheimer’s disease. J Neuropathol Exp Neurol 51:76–83. https://doi.org/10.1097/00005072-199201000-00009
Itoh N, Nagata S (1993) A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen. J Biol Chem 268:10932–10937
Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, Hosoki E, Kawashima-Morishima M, Lee HJ, Hama E, Sekine-Aizawa Y, Saido TC (2000) Identification of the major Aβ1–42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat Med 6:143–150. https://doi.org/10.1038/72237
Jaeger PA, Pickford F, Sun CH, Lucin KM, Masliah E, Wyss-Coray T (2010) Regulation of amyloid precursor protein processing by the Beclin 1 complex. PLoS One 5:e11102. https://doi.org/10.1371/journal.pone.0011102
Joshi P, Turola E, Ruiz A, Bergami A, Libera DD, Benussi L, Giussani P, Magnani G, Comi G, Legname G, Ghidoni R, Furlan R, Matteoli M, Verderio C (2014) Microglia convert aggregated amyloid-β into neurotoxic forms through the shedding of microvesicles. Cell Death Differ 21:582–593. https://doi.org/10.1038/cdd.2013.180
Jürgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D, Reed JC (1998) Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci U S A 95:4997–5002. https://doi.org/10.1073/pnas.95.9.4997
Kanamaru T, Kamimura N, Yokota T, Iuchi K, Nishimaki K, Takami S, Akashiba H, Shitaka Y, Katsura K, Kimura K, Ohta S (2015) Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer’s disease. Neurosci Lett 587:126–131. https://doi.org/10.1016/j.neulet.2014.12.033
Kantari C, Walczak H (2011) Caspase-8 and Bid: caught in the act between death receptors and mitochondria. Biochim Biophys Acta 1813:558–563. https://doi.org/10.1016/j.bbamcr.2011.01.026
Katayama T, Imaizumi K, Manabe T, Hitomi J, Kudo T, Tohyama M (2004) ‘nduction of neuronal death by ER stress in Alzheimer’s disease. J Chem Neuroanat 28:67–78. https://doi.org/10.1016/j.jchemneu.2003.12.004
Katsuda T, Oki K, Ochiya T (2015) Potential application of extracellular vesicles of human adipose tissue-derived mesenchymal stem cells in Alzheimer’s disease therapeutics. Methods Mol Biol 1212:171–181. https://doi.org/10.1007/7651_2014_98
Kern A, Roempp B, Prager K, Walter J, Behl C (2006) Down-regulation of endogenous amyloid precursor protein processing due to cellular aging. J Biol Chem 281:2405–2413. https://doi.org/10.1074/jbc.M505625200
Knafo S, Sánchez-Puelles C, Palomer E, Delgado I, Draffin JE, Mingo J, Wahle T, Kaleka K, Mou L, Pereda-Perez I, Klosi E, Faber EB, Chapman HM, Lozano-Montes L, Ortega-Molina A, Ordóñez-Gutiérrez L, Wandosell F, Viña J, Dotti CG, Hall RA, Pulido R, Gerges NZ, Chan AM, Spaller MR, Serrano M, Venero C, Esteban JA (2016) PTEN recruitment controls synaptic and cognitive function in Alzheimer’s models. Nat Neurosci 19:443–453. https://doi.org/10.1038/nn.4225
Kögel D, Deller T, Behl C (2012) Roles of amyloid precursor protein family members in neuroprotection, stress signaling and aging. Exp Brain Res 217:471–479. https://doi.org/10.1007/s00221-011-2932-4
Kojro E, Gimpl G, Lammich S, Marz W, Fahrenholz F (2001) Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the α-secretase ADAM 10. Proc Natl Acad Sci U S A 98:5815–5820. https://doi.org/10.1073/pnas.081612998
Landshamer S, Hoehn M, Barth N, Duvezin-Caubet S, Schwake G, Tobaben S, Kazhdan I, Becattini B, Zahler S, Vollmar A, Pellecchia M, Reichert A, Plesnila N, Wagner E, Culmsee C (2008) Bid-induced release of AIF from mitochondria causes immediate neuronal cell death. Cell Death Differ 15:1553–1563. https://doi.org/10.1038/cdd.2008.78
Lasierra-Cirujeda J, Coronel P, Aza M, Gimeno M (2013) Beta-amyloidolysis and glutathione in Alzheimer's disease. J Blood Med 4:31–38. https://doi.org/10.2147/jbm.s35496
Ledesma MD, Da Silva JS, Crassaerts K, Delacourte A, De Strooper B, Dotti CG (2000) Brain plasmin enhances APP α-cleavage and Aβ degradation and is reduced in Alzheimer’s disease brains. EMBO Rep 1:530–535. https://doi.org/10.1093/embo-reports/kvd107
Lee JH, Yu WH, Kumar A, Lee S, Mohan PS, Peterhoff CM, Wolfe DM, Martinez-Vicente M, Massey AC, Sovak G, Uchiyama Y, Westaway D, Cuervo AM, Nixon RA (2010) Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141:1146–1158. https://doi.org/10.1016/j.cell.2010.05.008
Lei P, Bai T, Sun Y (2019) Mechanisms of ferroptosis and relations with regulated cell death: a review. Front Physiol 10:139. https://doi.org/10.3389/fphys.2019.00139
Lemasters JJ (2017) Evolution of voltage-dependent anion channel function: from molecular sieve to governator to actuator of ferroptosis. Front Oncol 7:303. https://doi.org/10.3389/fonc.2017.00303
Leskovjan AC, Kretlow A, Lanzirotti A, Barrea R, Vogt S, Miller LM (2011) Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer’s disease. Neuroimage 55:32–38. https://doi.org/10.1016/j.neuroimage.2010.11.073
Lesné S, Ali C, Gabriel C, Croci N, MacKenzie ET, Glabe CG, Plotkine M, Marchand-Verrecchia C, Vivien D, Buisson A (2005) NMDA receptor activation inhibits α-secretase and promotes neuronal amyloid-β production. J Neurosci 25:9367–9377. https://doi.org/10.1523/jneurosci.0849-05.2005
Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 131:27–42. https://doi.org/10.1016/j.cell.2007.12.018
Lewerenz J, Ates G, Methner A, Conrad M, Maher P (2018) Oxytosis/ferroptosis-(Re-) emerging roles for oxidative stress-dependent non-apoptotic cell death in diseases of the central nervous system. Front Neurosci 12:214. https://doi.org/10.3389/fnins.2018.00214
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–489. https://doi.org/10.1016/S0092-8674(00)80434-1
Li J, McQuade T, Siemer AB, Napetschnig J, Moriwaki K, Hsiao YS, Damko E, Moquin D, Walz T, McDermott A, Chan FK, Wu H (2012) The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell 150:339–350. https://doi.org/10.1016/j.cell.2012.06.019
Li BH, Liao SQ, Yin YW, Long CY, Guo L, Cao XJ, Liu Y, Zhou Y, Gao CY, Zhang LL, Li JC (2015) Telmisartan-induced PPARγ activity attenuates lipid accumulation in VSMCs via induction of autophagy. Mol Biol Rep 42:179–186. https://doi.org/10.1007/s11033-014-3757-6
Liang C, Feng P, Ku B, Dotan I, Canaani D, Oh BH, Jung JU (2006) Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Nat Cell Biol 8:688–699. https://doi.org/10.1038/ncb1426
Linkermann A, Green DR (2014) Necroptosis. N Engl J Med 370:455–465. https://doi.org/10.1056/NEJMra1310050
Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501. https://doi.org/10.1016/S0092-8674(01)00237-9
Lovell JF, Billen LP, Bindner S, Shamas-Din A, Fradin C, Leber B, Andrews DW (2008) Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax. Cell 135:1074–1084. https://doi.org/10.1016/j.cell.2008.11.010
Lu PD, Harding HP, Ron D (2004) Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response. J Cell Biol 167:27–33. https://doi.org/10.1083/jcb.200408003
Ma T, Trinh MA, Wexler AJ, Bourbon C, Gatti E, Pierre P, Cavener DR, Klann E (2013) Suppression of eIF2α kinases alleviates Alzheimer’s disease-related plasticity and memory deficits. Nat Neurosci 16:1299–1305. https://doi.org/10.1038/nn.3486
Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741–752. https://doi.org/10.1038/nrm2239
Majewski N, Nogueira V, Bhaskar P, Coy PE, Skeen JE, Gottlob K, Chandel NS, Thompson CB, Robey RB, Hay N (2004) Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol Cell 16:819–830. https://doi.org/10.1016/j.molcel.2004.11.014
Man SM, Kanneganti TD (2015) Regulation of inflammasome activation. Immunol Rev 265:6–21. https://doi.org/10.1111/imr.12296
Masters SL, O’Neill LAJ (2011) Disease-associated amyloid and misfolded protein aggregates activate the inflammasome. Trends Mol Med 17:276–282. https://doi.org/10.1016/j.molmed.2011.01.005
Masud A, Mohapatra A, Lakhani SA, Ferrandino A, Hakem R, Flavell RA (2007) Endoplasmic reticulum stress-induced death of mouse embryonic fibroblasts requires the intrinsic pathway of apoptosis. J Biol Chem 282:14132–14139. https://doi.org/10.1074/jbc.M700077200
Matsuda N, Sato S, Shiba K, Okatsu K, Saisho K, Gautier CA, Sou YS, Saiki S, Kawajiri S, Sato F, Kimura M, Komatsu M, Hattori N, Tanaka K (2010) PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 189:211–221. https://doi.org/10.1083/jcb.200910140
Mattson MP (1997) Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol Rev 77:1081–1132. https://doi.org/10.1017/CBO9781107415324.004
Mattson MP (2004) Pathways towards and away from Alzheimer’s disease. Nature 430:631–639. https://doi.org/10.1038/nature02621
Mattson MP (2006) Neuronal life-and-death signaling, apoptosis, and neurodegenerative disorders. Antioxid Redox Signal 8:1997–2006. https://doi.org/10.1089/ars.2006.8.1997
Mattson MP, Cheng B, Davis D, Bryant K, Lieberburg I, Rydel RE (1992) Beta-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci 12:379–389. https://doi.org/10.1523/JNEUROSCI.12-02-00376.1992
Medema JP, Scaffidi C, Kischkel FC, Shevchenko A, Mann M, Krammer PH, Peter ME (1997) FLICE is activated by association with the CD95 death-inducing signaling complex (DISC). EMBO J 16:2794–2804. https://doi.org/10.1093/emboj/16.10.2794
Mehrpour M, Esclatine A, Beau I, Codogno P (2010) Overview of macroautophagy regulation in mammalian cells. Cell Res 20:748–762. https://doi.org/10.1038/cr.2010.82
Menéndez-González M, Pérez-Pinera P, Martínez-Rivera M, Calatayud MT, Blázquez Menes B (2005) APP processing and the APP-KPI domain involvement in the amyloid cascade. Neurodegener Dis 2:277–283. https://doi.org/10.1159/000092315
Mijaljica D, Prescott M, Devenish RJ (2011) V-ATPase engagement in autophagic processes. Autophagy 7:666–668. https://doi.org/10.4161/auto.7.6.15812
Mikulca JA, Nguyen V, Gajdosik DA, Teklu SG, Giunta EA, Lessa EA, Tran CH, Terak EC, Raffa RB (2014) Potential novel targets for Alzheimer pharmacotherapy: II. Update on secretase inhibitors and related approaches. J Clin Pharm Ther 39:25–37. https://doi.org/10.1111/jcpt.12112
Mizushima N (2005) Aβ generation in autophagic vacuoles. J Cell Biol 171:15–17. https://doi.org/10.1083/jcb.200508097
Mizushima N (2011) Autophagy in protein and organelle turnover. Cold Spring Harb Symp Quant Biol 76:397–402. https://doi.org/10.1101/sqb.2011.76.011023
Moir RD, Lynch T, Bush AI, Whyte S, Henry A, Portbury S, Multhaup G, Small DH, Tanzi RE, Beyreuther K, Masters CL (1998) Relative increase in Alzheimer’s disease of soluble forms of cerebral Aβ amyloid protein precursor containing the kunitz protease inhibitory domain. J Biol Chem 273:5013–5019. https://doi.org/10.1074/jbc.273.9.5013
Morley JE, Farr SA, Banks WA, Johnson SN, Yamada KA, Xu L (2010) A physiological role for amyloid-beta protein:enhancement of learning and memory. J Alzheimers Dis 19:441–449. https://doi.org/10.3233/JAD-2009-1230
Muresan Z, Muresan V (2007) The amyloid-beta precursor protein is phosphorylated via distinct pathways during differentiation, mitosis, stress, and degeneration. Mol Biol Cell 18:3835–3844. https://doi.org/10.1091/mbc.E06-07-0625
Murphy JM, Czabotar PE, Hildebrand JM, Lucet IS, Zhang JG, Alvarez-Diaz S, Lewis R, Lalaoui N, Metcalf D, Webb AI, Young SN, Varghese LN, Tannahill GM, Hatchell EC, Majewski IJ, Okamoto T, Dobson RC, Hilton DJ, Babon JJ, Nicola NA, Strasser A, Silke J, Alexander WS (2013) The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 39:443–453. https://doi.org/10.1016/j.immuni.2013.06.018
Nalivaeva NN, Turner AJ (2013) The amyloid precursor protein: a biochemical enigma in brain development, function and disease. FEBS Lett 587:2046–2054. https://doi.org/10.1016/j.febslet.2013.05.010
Narita M, Shimizu S, Ito T, Chittenden T, Lutz RJ, Matsuda H, Tsujimoto Y (1998) Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci U S A 95:14681–14686. https://doi.org/10.1073/pnas.95.25.14681
Neitemeier S, Jelinek A, Laino V, Hoffmann L, Eisenbach I, Eying R, Ganjam GK, Dolga AM, Oppermann S, Culmsee C (2017) BID links ferroptosis to mitochondrial cell death pathways. Redox Biol 12:558–570. https://doi.org/10.1016/j.redox.2017.03.007
Ngolab J, Trinh I, Rockenstein E, Mante M, Florio J, Trejo M, Masliah D, Adame A, Masliah E, Rissman RA (2017) Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathology. Acta Neuropathol Commun 5:46. https://doi.org/10.1186/s40478-017-0445-5
Nijholt DA, de Graaf TR, van Haastert ES, Oliveira AO, Berkers CR, Zwart R, Ovaa H, Baas F, Hoozemans JJ, Scheper W (2011) Endoplasmic reticulum stress activates autophagy but not the proteasome in neuronal cells: implications for Alzheimer’s disease. Cell Death Differ 18:1071–1081. https://doi.org/10.1038/cdd.2010.176
Nikolaev A, McLaughlin T, O'Leary DD, Tessier-Lavigne M (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457:981–989. https://doi.org/10.1038/nature07767
Nordstedt C, Caporaso GL, Thyberg J, Gandy SE, Greengard P (1993) Identification of the Alzheimer beta/A4 amyloid precursor protein in clathrin-coated vesicles purified from PC12 cells. J Biol Chem 268:608–612
O'Brien RJ, Wong PC (2010) Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci 34:185–204. https://doi.org/10.1146/annurev-neuro-061010-113613
O'Connor T, Sadleir KR, Maus E, Velliquette RA, Zhao J, Cole SL, Eimer WA, Hitt B, Bembinster LA, Lammich S, Lichtenthaler SF, Hébert SS, De Strooper B, Haass C, Bennett DA, Vassar R (2008) Phosphorylation of the translation initiation factor eIF2α increases BACE1 levels and promotes amyloidogenesis. Neuron 60:988–1009. https://doi.org/10.1016/j.neuron.2008.10.047
Ohgami T, Kitamoto T, Tateishi J (1992) Alzheimer’s amyloid precursor protein accumulates within axonal swellings in human brain lesions. Neurosci Lett 136:75–78. https://doi.org/10.1016/0304-3940(92)90651-M
Ohsawa I, Takamura C, Morimoto T, Ishiguro M, Kohsaka S (1999) Amino-terminal region of secreted form of amyloid precursor protein stimulates proliferation of neural stem cells. Eur J Neurosci 11:1907–1913. https://doi.org/10.1046/j.1460-9568.1999.00601.x
Paesler K, Xie K, Hettich MM, Siwek ME, Ryan DP, Schröder S, Papazoglou A, Broich K, Müller R, Trog A, Garthe A, Kempermann G, Weiergräber M, Ehninger D (2015) Limited effects of an eIF2α S51A allele on neurological impairments in the 5xFAD mouse model of Alzheimer’s disease. Neural Plast 2015:825157. https://doi.org/10.1155/2015/825157
Pakos-Zebrucka K, Koryga I, Mnich K, Ljujic M, Samali A, Gorman AM (2016) The integrated stress response. EMBO Rep 17:1374–1395. https://doi.org/10.15252/embr.201642195
Palmert MR, Podlisny MB, Golde TE, Cohen ML, Kovacs DM, Tanzi RE, Gusella JF, Whitehouse PJ, Witker DS, Oltersdorf T (1989) The beta amyloid protein precursor: mRNAs, membrane-associated forms, and soluble derivatives. Prog Clin Biol Res 317:971–984
Pan G, Bauer JH, Haridas V, Wang S, Liu D, Yu G, Vincenz C, Aggarwal BB, Ni J, Dixit VM (1998) Identification and functional characterization of DR6, a novel death domain-containing TNF receptor. FEBS Lett 431:351–356. https://doi.org/10.1016/S0014-5793(98)00791-1
Panza F, Frisardi V, Solfrizzi V, Imbimbo BP, Logroscino G, Santamato A, Greco A, Seripa D, Pilotto A (2011) Interacting with γ-secretase for treating Alzheimer’s disease: from inhibition to modulation. Curr Med Chem 18:5430–5447. https://doi.org/10.2174/092986711798194351
Parvathy S, Ehrlich M, Pedrini S, Diaz N, Refolo L, Buxbaum JD, Bogush A, Petanceska S, Gandy S (2004) Atorvastatin-induced activation of Alzheimer’s α secretase is resistant to standard inhibitors of protein phosphorylation-regulated ectodomain shedding. J Neurochem 90:1005–1010. https://doi.org/10.1111/j.1471-4159.2004.02521.x
Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD, Levine B (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122:927–939. https://doi.org/10.1016/j.cell.2005.07.002
Petrie EJ, Sandow JJ, Jacobsen AV, Smith BJ, Griffin MDW, Lucet IS, Dai W, Young SN, Tanzer MC, Wardak A, Liang LY, Cowan AD, Hildebrand JM, Kersten WJA, Lessene G, Silke J, Czabotar PE, Webb AI, Murphy JM (2018) Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis. Nat Commun 9:2422. https://doi.org/10.1038/s41467-018-04714-7
Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger PA, Small S, Spencer B, Rockenstein E, Levine B, Wyss-Coray T (2008) The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice. J Clin Invest 118:2190–2199. https://doi.org/10.1172/JCI33585
Plant LD, Boyle JP, Smith IF, Peers C, Pearson HA (2003) The production of amyloid beta peptide is a critical requirement for the viability of central neurons. J Neurosci 23:5531–5535. https://doi.org/10.1523/JNEUROSCI.23-13-05531.2003
Popp J, Lewczuk P, Kölsch H, Meichsner S, Maier W, Kornhuber J, Jessen F, Lütjohann D (2012) Cholesterol metabolism is associated with soluble amyloid precursor protein production in Alzheimer’s disease. J Neurochem 123:310–316. https://doi.org/10.1111/j.1471-4159.2012.07893.x
Puzzo D, Privitera L, Leznik E, Fà M, Staniszewski A, Palmeri A, Arancio O (2008) Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. J Neurosci 28:14537–14545. https://doi.org/10.1523/JNEUROSCI.2692-08.2008
Rajendran L, Honsho M, Zahn TR, Keller P, Geiger KD, Verkade P, Simons K (2006) Alzheimer’s disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci U S A 103:11172–11177. https://doi.org/10.1073/pnas.0603838103
Rajendran L, Bali J, Barr MM, Court FA, Krämer-Albers EM, Picou F, Raposo G, van der Vos KE, van Niel G, Wang J, Breakefield XO (2014) Emerging roles of extracellular vesicles in the nervous system. J Neurosci 34:15482–15489. https://doi.org/10.1523/JNEUROSCI.3258-14.2014
Rathinam VAK, Fitzgerald KA (2016) Inflammasome complexes: emerging mechanisms and effector functions. Cell 165:792–800. https://doi.org/10.1016/j.cell.2016.03.046
Reddy PH, Beal MF (2008) Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer’s disease. Trends Mol Med 14:45–53. https://doi.org/10.1016/j.molmed.2007.12.002
Redza-Dutordoir M, Averill-Bates DA (2016) Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 1863:2977–2992. https://doi.org/10.1016/j.bbamcr.2016.09.012
Reinhard C, Hébert SS, De Strooper B (2005) The amyloid-beta precursor protein: integrating structure with biological function. EMBO J 24:3996–4006. https://doi.org/10.1038/sj.emboj.7600860
Reinhardt S, Schuck F, Grösgen S, Riemenschneider M, Hartmann T, Postina R, Grimm M, Endres K (2014) Unfolded protein response signaling by transcription factor XBP-1 regulates ADAM10 and is affected in Alzheimer’s disease. FASEB J 28:978–997. https://doi.org/10.1096/fj.13-234864
Reitz C (2012) Alzheimer’s disease and the amyloid cascade hypothesis: a critical review. Int J Alzheimers Dis 2012:369808. https://doi.org/10.1155/2012/369808
Roberts GW, Gentleman SM, Lynch A, Murray L, Landon M, Graham DI (1994) β3 Amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 57:419–425. https://doi.org/10.1136/jnnp.57.4.419
Rong Y, Liu M, Ma L, Du W, Zhang H, Tian Y, Cao Z, Li Y, Ren H, Zhang C, Li L, Chen S, Xi J, Yu L (2012) Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation. Nat Cell Biol 14:924–934. https://doi.org/10.1038/ncb2557
Rouschop KM, van den Beucken T, Dubois L, Niessen H, Bussink J, Savelkouls K, Keulers T, Mujcic H, Landuyt W, Voncken JW, Lambin P, van der Kogel AJ, Koritzinsky M, Wouters BG (2010) The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. J Clin Invest 120:127–141. https://doi.org/10.1172/JCI40027
Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Liao Z, Lieberburg I, Motter R, Mutter L, Soriano F, Shopp G, Vasquez N, Vandevert C, Walker S, Wogulis M, Yednock T, Games D, Seubert P (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173–177. https://doi.org/10.1038/22124
Schulze-Osthoff K, Ferrari D, Los M, Wesselborg S, Peter ME (1998) Apoptosis signaling by death receptors. Eur J Biochem 254:439–459. https://doi.org/10.1046/j.1432-1327.1998.2540439.x
Selkoe DJ (1998) The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer’s disease. Trends Cell Biol 8:447–453. https://doi.org/10.1016/S0962-8924(98)01363-4
Sennvik K, Bogdanovic N, Volkmann I, Fastbom J, Benedikz E (2004) Beta-secretase-cleaved amyloid precursor protein in Alzheimer brain: a morphologic study. J Cell Mol Med 8:127–134
Shah R, Shchepinov MS, Pratt DA (2018) Resolving the role of lipoxygenases in the initiation and execution of ferroptosis. ACS Cent Sci 4:387–396. https://doi.org/10.1021/acscentsci.7b00589
Shalini S, Dorstyn L, Dawar S, Kumar S (2015) Old, new and emerging functions of caspases. Cell Death Differ 22:526–539. https://doi.org/10.1038/cdd.2014.216
Shi J, Gao W, Shao F (2017) Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci 42:245–254. https://doi.org/10.1016/j.tibs.2016.10.004
Shimizu S, Matsuoka Y, Shinohara Y, Yoneda Y, Tsujimoto Y (2001) Essential role of voltage-dependent anion channel in various forms of apoptosis in mammalian cells. J Cell Biol 152:237–250. https://doi.org/10.1083/jcb.152.2.237
Shimizu S, Konishi A, Nishida Y, Mizuta T, Nishina H, Yamamoto A, Tsujimoto Y (2010) Involvement of JNK in the regulation of autophagic cell death. Oncogene 29:2070–2082. https://doi.org/10.1038/onc.2009.487
Shintoku R, Takigawa Y, Yamada K, Kubota C, Yoshimoto Y, Takeuchi T, Koshiishi I, Torii S (2017) Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3. Cancer Sci 108:2187–2194. https://doi.org/10.1111/cas.13380
Shoshan-Barmatz V, Maldonado EN, Krelin Y (2017) VDAC1 at the crossroads of cell metabolism, apoptosis and cell stress. Cell Stress 1:11–36. https://doi.org/10.15698/cst2017.10.104
Sirk D, Zhu Z, Wadia JS, Shulyakova N, Phan N, Fong J, Mills LR (2007) Chronic exposure to sub-lethal beta-amyloid (Aβ) inhibits the import of nuclear-encoded proteins to mitochondria in differentiated PC12 cells. J Neurochem 103:1989–2003. https://doi.org/10.1111/j.1471-4159.2007.04907.x
Sisodia SS (1992) Beta-amyloid precursor protein cleavage by a membrane-bound protease. Proc Natl Acad Sci U S A 89:6075–6079. https://doi.org/10.1073/pnas.89.13.6075
Smith MI, Deshmukh M (2007) Endoplasmic reticulum stress-induced apoptosis requires bax for commitment and Apaf-1 for execution in primary neurons. Cell Death Differ 14:1011–1019. https://doi.org/10.1038/sj.cdd.4402089
Smith MA, Harris PL, Sayre LM, Perry G (1997) Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci U S A 94:9866–9868. https://doi.org/10.1073/pnas.94.18.9866
Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, Nairn AC, Salter MW, Lombroso PJ, Gouras GK, Greengard P (2005) Regulation of NMDA receptor trafficking by amyloid-β. Nat Neurosci 8:1051–1058. https://doi.org/10.1038/nn1503
Soupene E, Fyrst H, Kuypers FA (2008) Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes. Proc Natl Acad Sci U S A 105:88–93. https://doi.org/10.1073/pnas.0709737104
Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascón S, Hatzios SK, Kagan VE, Noel K, Jiang X, Linkermann A, Murphy ME, Overholtzer M, Oyagi A, Pagnussat GC, Park J, Ran Q, Rosenfeld CS, Salnikow K, Tang D, Torti FM, Torti SV, Toyokuni S, Woerpel KA, Zhang DD (2017) Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171:273–285. https://doi.org/10.1016/j.cell.2017.09.021
Sun X, Yin J, Starovasnik MA, Fairbrother WJ, Dixit VM (2002) Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3. J Biol Chem 277:9505–9511. https://doi.org/10.1074/jbc.M109488200
Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X, Wang X (2012) Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148:213–227. https://doi.org/10.1016/j.cell.2011.11.031
Tam AB, Mercado EL, Hoffmann A, Niwa M (2012) ER stress activates NF-κB by integrating functions of basal IKK activity, IRE1 and PERK. PLoS One 7:e45078. https://doi.org/10.1371/journal.pone.0045078
Tan S, Schubert D, Maher P (2001) Oxytosis: a novel form of programmed cell death. Curr Top Med Chem 1:497–506. https://doi.org/10.2174/1568026013394741
Tan MS, Tan L, Jiang T, Zhu XC, Wang HF, Jia CD, Yu JT (2014) Amyloid-β induces NLRP1-dependent neuronal pyroptosis in models of Alzheimer’s disease. Cell Death Dis 5:e1382. https://doi.org/10.1038/cddis.2014.348
Tanaka S, Shiojiri S, Takahashi Y, Kitaguchi N, Ito H, Kameyama M, Kimura J, Nakamura S, Ueda K (1989) Tissue-specific expression of three types of β-protein precursor mRNA: enhancement of protease inhibitor-harboring types in Alzheimer’s disease brain. Biochem Biophys Res Commun 165:1406–1414. https://doi.org/10.1016/0006-291X(89)92760-5
Tanida I (2011) Autophagosome formation and molecular mechanism of autophagy. Antioxid Redox Signal 14:2201–2214. https://doi.org/10.1089/ars.2010.3482
Taylor JP, Hardy J, Fischbeck KH (2002) Toxic proteins in neurodegenerative disease. Science 296:1991–1995. https://doi.org/10.1126/science.1067122
Tekirdag K, Cuervo AM (2018) Chaperone-mediated autophagy and endosomal microautophagy: joint by a chaperone. J Biol Chem 293:5414–5424. https://doi.org/10.1074/jbc.R117.818237
Théry C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2:569–579. https://doi.org/10.1038/nri855
Thinakaran G, Koo EH (2008) Amyloid precursor protein trafficking, processing, and function. J Biol Chem 283:29615–29619. https://doi.org/10.1074/jbc.R800019200
Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316. https://doi.org/10.1126/science.281.5381.1312
Tönnies E, Trushina E (2017) Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. J Alzheimers Dis 57:1105–1121. https://doi.org/10.3233/JAD-161088
Tsujimoto Y, Shimizu S (2000) VDAC regulation by the Bcl-2 family of proteins. Cell Death Differ 152:237–250. https://doi.org/10.1038/sj.cdd.4400780
Uenaka K, Nakano M, Willis BA, Friedrich S, Ferguson-Sells L, Dean RA, Ieiri I, Siemers ER (2012) Comparison of pharmacokinetics, pharmacodynamics, safety, and tolerability of the amyloid β monoclonal antibody solanezumab in japanese and white patients with mild to moderate Alzheimer disease. Clin Neuropharmacol 35:25–29. https://doi.org/10.1097/WNF.0b013e31823a13d3
Upton JP, Wang L, Han D, Wang ES, Huskey NE, Lim L, Truitt M, McManus MT, Ruggero D, Goga A, Papa FR, Oakes SA (2012) IRE1α cleaves select microRNAs during ER stress to derepress translation of proapoptotic caspase-2. Science 338:818–822. https://doi.org/10.1126/science.1226191
Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP, Ron D (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287:664–666. https://doi.org/10.1126/science.287.5453.664
Vanden Berghe T, Grootjans S, Goossens V, Dondelinger Y, Krysko DV, Takahashi N, Vandenabeele P (2013) Determination of apoptotic and necrotic cell death in vitro and in vivo. Methods 61:117–129. https://doi.org/10.1016/j.ymeth.2013.02.011
Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11:700–714. https://doi.org/10.1038/nrm2970
Vetrivel KS, Thinakaran G (2006) Amyloidogenic processing of beta-amyloid precursor protein in intracellular compartments. Neurology 66:S69–S73. https://doi.org/10.1212/01.wnl.0000192107.17175.39
Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, Ames D, Rowe CC, Masters CL, Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group (2013) Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol 12:357–367. https://doi.org/10.1016/S1474-4422(13)70044-9
Vlassov AV, Magdaleno S, Setterquist R, Conrad R (2012) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 1820:940–948. https://doi.org/10.1016/j.bbagen.2012.03.017
Vo DK, Urano Y, Takabe W, Saito Y, Noguchi N (2015) 24(S)-Hydroxycholesterol induces RIPK1-dependent but MLKL-independent cell death in the absence of caspase-8. Steroids 99:230–237. https://doi.org/10.1016/j.steroids.2015.02.007
Wahlster L, Arimon M, Nasser-Ghodsi N, Post KL, Serrano-Pozo A, Uemura K, Berezovska O (2013) Presenilin-1 adopts pathogenic conformation in normal aging and in sporadic Alzheimer’s disease. Acta Neuropathol 125:187–199. https://doi.org/10.1007/s00401-012-1065-6
Wang H, Sun L, Su L, Rizo J, Liu L, Wang LF, Wang FS, Wang X (2014) Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell 54:133–146. https://doi.org/10.1016/j.molcel.2014.03.003
Wang Y, Balaji V, Kaniyappan S, Krüger L, Irsen S, Tepper K, Chandupatla R, Maetzler W, Schneider A, Mandelkow E, Mandelkow EM (2017) The release and trans-synaptic transmission of Tau via exosomes. Mol Neurodegener 12:5. https://doi.org/10.1186/s13024-016-0143-y
Ward RJ, Zucca FA, Duyn JH, Crichton RR, Zecca L (2014) The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol 13:1045–1060. https://doi.org/10.1016/S1474-4422(14)70117-6
Wei Y, Pattingre S, Sinha S, Bassik M, Levine B (2008) JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell 30:678–688. https://doi.org/10.1016/j.molcel.2008.06.001
Wilhelmus MM, van der Pol SM, Jansen Q, Witte ME, van der Valk P, Rozemuller AJ, Drukarch B, de Vries HE, Van Horssen J (2011) Association of Parkinson disease-related protein PINK1 with Alzheimer disease and multiple sclerosis brain lesions. Free Radic Biol Med 50:469–476. https://doi.org/10.1016/j.freeradbiomed.2010.11.033
Willis SN, Adams JM (2005) Life in the balance: how BH3-only proteins induce apoptosis. Curr Opin Cell Biol 17:617–625. https://doi.org/10.1016/j.ceb.2005.10.001
Wilson NS, Dixit V, Ashkenazi A (2009) Death receptor signal transducers: nodes of coordination in immune signaling networks. Nat Immunol 10:348–355. https://doi.org/10.1038/ni.1714
Wolozin B (2002) A fluid connection: cholesterol and Aβ. Proc Natl Acad Sci U S A 98:5371–5373. https://doi.org/10.1073/pnas.101123198
Wolozin B (2004) Cholesterol and the biology of Alzheimer’s disease. Neuron 41:7–10. https://doi.org/10.1016/S0896-6273(03)00840-7
Woltjer RL, Nghiem W, Maezawa I, Milatovic D, Vaisar T, Montine KS, Montine TJ (2005) Role of glutathione in intracellular amyloid-α precursor protein/ carboxy-terminal fragment aggregation and associated cytotoxicity. J Neurochem 93:1047–1056. https://doi.org/10.1111/j.1471-4159.2005.03109.x
Wu L, Rosa-Neto P, Hsiung GY, Sadovnick AD, Masellis M, Black SE, Jia J, Gauthier S (2012) Early-onset familial alzheimer’s disease (EOFAD). Can J Neurol Sci 39:436–445. https://doi.org/10.1017/S0317167100013949
Xie T, Peng W, Yan C, Wu J, Gong X, Shi Y (2013) Structural insights into RIP3-mediated necroptotic signaling. Cell Rep 5:70–78. https://doi.org/10.1016/j.celrep.2013.08.044
Xiong H, Callaghan D, Jones A, Walker DG, Lue LF, Beach TG, Sue LI, Woulfe J, Xu H, Stanimirovic DB, Zhang W (2008) Cholesterol retention in Alzheimer’s brain is responsible for high β- and γ-secretase activities and Aβ production. Neurobiol Dis 29:422–437. https://doi.org/10.1016/j.nbd.2007.10.005
Xu H, Sweeney D, Wang R, Thinakaran G, Lo AC, Sisodia SS, Greengard P, Gandy S (1997) Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation. Proc Natl Acad Sci U S A 94:3748–3752. https://doi.org/10.1021/js960333n
Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, Wolpaw AJ, Smukste I, Peltier JM, Boniface JJ, Smith R, Lessnick SL, Sahasrabudhe S, Stockwell BR (2007) RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 447:864–868. https://doi.org/10.1038/nature05859
Yakovlev AG, Faden AI (2004) Mechanisms of neural cell death: implications for development of neuroprotective treatment strategies. NeuroRx 1:5–16. https://doi.org/10.1602/neurorx.1.1.5
Yamanaka K, Urano Y, Takabe W, Saito Y, Noguchi N (2014) Induction of apoptosis and necroptosis by 24(S)-hydroxycholesterol is dependent on activity of acyl-CoA:cholesterol acyltransferase 1. Cell Death Dis 5:e990. https://doi.org/10.1038/cddis.2013.524
Yang WS, Stockwell BR (2016) Ferroptosis: death by lipid peroxidation. Trends Cell Biol 26:165–176. https://doi.org/10.1016/j.tcb.2015.10.014
Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB, Brown LM, Girotti AW, Cornish VW, Schreiber SL, Stockwell BR (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156:317–331. https://doi.org/10.1016/j.cell.2013.12.010
Yang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR (2016) Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci U S A 113:E4966–E4975. https://doi.org/10.1073/pnas.1603244113
Yang SH, Lee DK, Shin J, Lee S, Baek S, Kim J, Jung H, Hah JM, Kim Y (2017) Nec-1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice. EMBO Mol Med 9:61–77. https://doi.org/10.15252/emmm.201606566
Yeh WC, Shahinian A, Speiser D, Kraunus J, Billia F, Wakeham A, de la Pompa JL, Ferrick D, Hum B, Iscove N, Ohashi P, Rothe M, Goeddel DV, Mak TW (1997) Early lethality, functional NF-κB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice. Immunity 7:715–725. https://doi.org/10.1016/S1074-7613(00)80391-X
Yin J, Zhao F, Chojnacki JE, Fulp J, Klein WL, Zhang S, Zhu X (2018) NLRP3 inflammasome inhibitor ameliorates amyloid pathology in a mouse model of Alzheimer’s disease. Mol Neurobiol 55:1977–1987. https://doi.org/10.1007/s12035-017-0467-9
Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, Tohyama M (2001) Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem 276:13935–13940. https://doi.org/10.1074/jbc.M010677200
Yoshida H, Okada T, Haze K, Yanagi H, Yura T, Negishi M, Mori K (2000) ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Mol Cell Biol 20:6755–6767. https://doi.org/10.1128/mcb.20.18.6755-6767.2000
Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K (2001) XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107:881–891. https://doi.org/10.1016/S0092-8674(01)00611-0
Yu L (2004) Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304:1500–1502. https://doi.org/10.1126/science.1096645
Yu Z, Luo H, Fu W, Mattson MP (1999) The endoplasmic reticulum stress-responsive protein GRP78 protects neurons against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis. Exp Neurol 155:302–314. https://doi.org/10.1006/exnr.1998.7002
Yu WH, Kumar A, Peterhoff C, Shapiro Kulnane L, Uchiyama Y, Lamb BT, Cuervo AM, Nixon RA (2004) Autophagic vacuoles are enriched in amyloid precursor protein-secretase activities: implications for β-amyloid peptide over-production and localization in Alzheimer’s disease. Int J Biochem Cell Biol 36:2531–2540. https://doi.org/10.1016/j.biocel.2004.05.010
Yu WH, Cuervo AM, Kumar A, Peterhoff CM, Schmidt SD, Lee JH, Mohan PS, Mercken M, Farmery MR, Tjernberg LO, Jiang Y, Duff K, Uchiyama Y, Näslund J, Mathews PM, Cataldo AM, Nixon RA (2005) Macroautophagy - a novel β-amyloid peptide-generating pathway activated in Alzheimer’s disease. J Cell Biol 171:87–98. https://doi.org/10.1083/jcb.200505082
Yu W, Sun Y, Guo S, Lu B (2011) The PINK1/Parkin pathway regulates mitochondrial dynamics and function in mammalian hippocampal and dopaminergic neurons. Hum Mol Genet 20:3227–3240. https://doi.org/10.1093/hmg/ddr235
Yuyama K, Sun H, Mitsutake S, Igarashi Y (2012) Sphingolipid-modulated exosome secretion promotes clearance of amyloid-β by microglia. J Biol Chem 287:10977–10989. https://doi.org/10.1074/jbc.M111.324616
Yuyama K, Sun H, Sakai S, Mitsutake S, Okada M, Tahara H, Furukawa J, Fujitani N, Shinohara Y, Igarashi Y (2014) Decreased amyloid-β pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. J Biol Chem 289:24488–24498. https://doi.org/10.1074/jbc.M114.577213
Yuyama K, Sun H, Usuki S, Sakai S, Hanamatsu H, Mioka T, Kimura N, Okada M, Tahara H, Furukawa J, Fujitani N, Shinohara Y, Igarashi Y (2015) A potential function for neuronal exosomes: sequestering intracerebral amyloid-β peptide. FEBS Lett 589:84–88. https://doi.org/10.1016/j.febslet.2014.11.027
Zeng L, Li T, Xu DC, Liu J, Mao G, Cui MZ, Fu X, Xu X (2012) Death receptor 6 induces apoptosis not through type I or type II pathways, but via a unique mitochondria-dependent pathway by interacting with bax protein. J Biol Chem 287:29125–29133. https://doi.org/10.1074/jbc.M112.362038
Zhang H, Ma Q, Zhang YW, Xu H (2012) Proteolytic processing of Alzheimer’s β-amyloid precursor protein. J Neurochem 120:9–21. https://doi.org/10.1111/j.1471-4159.2011.07519.x
Zhang L, Fang Y, Cheng X, Lian Y, Xu H, Zeng Z, Zhu H (2017) TRPML1 participates in the progression of Alzheimer’s disease by regulating the PPARγ/AMPK/Mtor signalling pathway. Cell Physiol Biochem 43:2446–2456. https://doi.org/10.1159/000484449
Zhao J, Jitkaew S, Cai Z, Choksi S, Li Q, Luo J, Liu ZG (2012) Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc Natl Acad Sci U S A 109:5322–5327. https://doi.org/10.1073/pnas.1200012109
Zheng T, Pu J, Chen Y, Mao Y, Guo Z, Pan H, Zhang L, Zhang H, Sun B, Zhang B (2017) Plasma exosomes spread and cluster around beta-amyloid plaques in an animal model of Alzheimer’s disease. Front Aging Neurosci 9:12. https://doi.org/10.3389/fnagi.2017.00012
Zhou F, van Laar T, Huang H, Zhang L (2011) APP and APLP1 are degraded through autophagy in response to proteasome inhibition in neuronal cells. Protein Cell 2:377–383. https://doi.org/10.1007/s13238-011-1047-9
Zhu X, Raina AK, Lee HG, Casadesus G, Smith MA, Perry G (2004) Oxidative stress signalling in Alzheimer’s disease. Brain Res 1000:32–39. https://doi.org/10.1016/j.brainres.2004.01.012
Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H, Stevens JL, Ron D (1998) CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 12:982–995. https://doi.org/10.1101/gad.12.7.982
Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90:405–413. https://doi.org/10.1016/S0092-8674(00)80501-2
Acknowledgements
The authors would like to acknowledge the support of Ministry of Higher Education Malaysia under project FRGS/1/2016/SKK08/IMU/03/3.
Author information
Authors and Affiliations
Contributions
YQL wrote the manuscript. KYN, SMC, APKL and RYK critically reviewed the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Leong, Y.Q., Ng, K.Y., Chye, S.M. et al. Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death. Metab Brain Dis 35, 11–30 (2020). https://doi.org/10.1007/s11011-019-00516-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-019-00516-y