Abstract
A common feature in most neurodegenerative diseases and aging is the progressive accumulation of damaged proteins. Proteins are essential for all crucial biological functions. Under some notorious conditions, proteins loss their three dimensional native conformations and are converted into disordered aggregated structures. Such changes rise into pathological conditions and eventually cause serious protein conformation disorders. Protein aggregation and inclusion bodies formation mediated multifactorial proteotoxic stress has been reported in the progression of Parkinson’s disease (PD), Huntington’s disease (HD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Prion disease. Ongoing studies have been remarkably informative in providing a systematic outlook for better understanding the concept and fundamentals of protein misfolding and aggregations. However, the precise role of protein quality control system and precursors of this mechanism remains elusive. In this review, we highlight recent insights and discuss emerging cytoprotective strategies of cellular protein quality control system implicated in protein deposition diseases. Our current review provides a clear, understandable framework of protein quality control system that may offer the more suitable therapeutic strategies for protein-associated diseases.
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Brandman O, Stewart-Ornstein J, Wong D, Larson A, Williams CC, Li GW, Zhou S, King D, Shen PS, Weibezahn J, Dunn JG, Rouskin S, Inada T, Frost A, Weissman JS (2012) A ribosome-bound quality control complex triggers degradation of nascent peptides and signals translation stress. Cell 151(5):1042–1054. doi:10.1016/j.cell.2012.10.044
Beckmann R, Bubeck D, Grassucci R, Penczek P, Verschoor A, Blobel G, Frank J (1997) Alignment of conduits for the nascent polypeptide chain in the ribosome-Sec61 complex. Science 278(5346):2123–2126
Chen B, Retzlaff M, Roos T, Frydman J (2011) Cellular strategies of protein quality control. Cold Spring Harb Perspect Biol 3(8):a004374. doi:10.1101/cshperspect.a004374
Chiti F, Dobson CM (2006) Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366. doi:10.1146/annurev.biochem.75.101304.123901
Gregersen N, Bross P (2010) Protein misfolding and cellular stress: an overview. Methods Mol Biol 648:3–23. doi:10.1007/978-1-60761-756-3_1
Ross CA, Poirier MA (2004) Protein aggregation and neurodegenerative disease. Nat Med 10(Suppl):S10–S17. doi:10.1038/nm1066
Dobson CM (2003) Protein folding and misfolding. Nature 426(6968):884–890. doi:10.1038/nature02261
Selkoe DJ (2003) Folding proteins in fatal ways. Nature 426(6968):900–904. doi:10.1038/nature02264
Fulda S, Gorman AM, Hori O, Samali A (2010) Cellular stress responses: cell survival and cell death. Int J Cell Biol 2010:214074. doi:10.1155/2010/214074
Forman MS, Trojanowski JQ, Lee VM (2004) Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat Med 10(10):1055–1063. doi:10.1038/nm1113
Layfield R, Lowe J, Bedford L (2005) The ubiquitin–proteasome system and neurodegenerative disorders. Essays Biochem 41:157–171. doi:10.1042/EB0410157
Dennissen FJ, Kholod N, van Leeuwen FW (2012) The ubiquitin proteasome system in neurodegenerative diseases: culprit, accomplice or victim? Prog Neurobiol 96(2):190–207. doi:10.1016/j.pneurobio.2012.01.003
Glickman MH, Ciechanover A (2002) The ubiquitin–proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82(2):373–428. doi:10.1152/physrev.00027.2001
Voges D, Zwickl P, Baumeister W (1999) The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 68:1015–1068. doi:10.1146/annurev.biochem.68.1.1015
Chhangani D, Joshi AP, Mishra A (2012) E3 ubiquitin ligases in protein quality control mechanism. Mol Neurobiol 45(3):571–585. doi:10.1007/s12035-012-8273-x
Ardley HC, Robinson PA (2004) The role of ubiquitin–protein ligases in neurodegenerative disease. Neurodegener Dis 1(2–3):71–87. doi:10.1159/000080048
Yonashiro R, Sugiura A, Miyachi M, Fukuda T, Matsushita N, Inatome R, Ogata Y, Suzuki T, Dohmae N, Yanagi S (2009) Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates mutant SOD1-induced reactive oxygen species generation. Mol Biol Cell 20(21):4524–4530. doi:10.1091/mbc.E09-02-0112
Mishra A, Maheshwari M, Chhangani D, Fujimori-Tonou N, Endo F, Joshi AP, Jana NR, Yamanaka K (2013) E6-AP association promotes SOD1 aggresomes degradation and suppresses toxicity. Neurobiol Aging. doi:10.1016/j.neurobiolaging.2012.08.016
Niwa J, Ishigaki S, Hishikawa N, Yamamoto M, Doyu M, Murata S, Tanaka K, Taniguchi N, Sobue G (2002) Dorfin ubiquitylates mutant SOD1 and prevents mutant SOD1-mediated neurotoxicity. J Biol Chem 277(39):36793–36798. doi:10.1074/jbc.M206559200
Urushitani M, Kurisu J, Tateno M, Hatakeyama S, Nakayama K, Kato S, Takahashi R (2004) CHIP promotes proteasomal degradation of familial ALS-linked mutant SOD1 by ubiquitinating Hsp/Hsc70. J Neurochem 90(1):231–244. doi:10.1111/j.1471-4159.2004.02486.x
Ying Z, Wang H, Fan H, Zhu X, Zhou J, Fei E, Wang G (2009) Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation. Hum Mol Genet 18(22):4268–4281. doi:10.1093/hmg/ddp380
Miyazaki K, Fujita T, Ozaki T, Kato C, Kurose Y, Sakamoto M, Kato S, Goto T, Itoyama Y, Aoki M, Nakagawara A (2004) NEDL1, a novel ubiquitin–protein isopeptide ligase for dishevelled-1, targets mutant superoxide dismutase-1. J Biol Chem 279(12):11327–11335. doi:10.1074/jbc.M312389200
Ren Y, Zhao J, Feng J (2003) Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation. J Neurosci Off J Soc Neurosci 23(8):3316–3324
Imai Y, Soda M, Hatakeyama S, Akagi T, Hashikawa T, Nakayama K, Takahashi R (2002) CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity. Mol Cell 10(1):55–67. doi:10.1016/s1097-2765(02)00583-x
Kalia L, Kalia S, Chau H, Lozano A, Hyman B, McLean P (2011) Ubiquitinylation of α-synuclein by carboxyl terminus Hsp70-interacting protein (CHIP) is regulated by Bcl-2-associated athanogene 5 (BAG5). PLoS One 6(2): doi:10.1371/journal.pone.0014695
Mulherkar SA, Sharma J, Jana NR (2009) The ubiquitin ligase E6-AP promotes degradation of alpha-synuclein. J Neurochem 110(6):1955–1964. doi:10.1111/j.1471-4159.2009.06293.x
Skinner P, Koshy B, Cummings C, Klement I, Helin K, Servadio A, Zoghbi H, Orr H (1997) Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures. Nature 389(6654):971–974. doi:10.1038/40153
Ross C (1997) Intranuclear neuronal inclusions: a common pathogenic mechanism for glutamine-repeat neurodegenerative diseases? Neuron 19(6):1147–1150. doi:10.1016/s0896-6273(00)80405-5
Mishra A, Dikshit P, Purkayastha S, Sharma J, Nukina N, Jana NR (2008) E6-AP promotes misfolded polyglutamine proteins for proteasomal degradation and suppresses polyglutamine protein aggregation and toxicity. J Biol Chem 283(12):7648–7656. doi:10.1074/jbc.M706620200
Garyali P, Siwach P, Singh PK, Puri R, Mittal S, Sengupta S, Parihar R, Ganesh S (2009) The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin–proteasome system. Hum Mol Genet 18(4):688–700. doi:10.1093/hmg/ddn398
Jana NR, Dikshit P, Goswami A, Kotliarova S, Murata S, Tanaka K, Nukina N (2005) Co-chaperone CHIP associates with expanded polyglutamine protein and promotes their degradation by proteasomes. J Biol Chem 280(12):11635–11640. doi:10.1074/jbc.M412042200
Tsai YC, Fishman PS, Thakor NV, Oyler GA (2003) Parkin facilitates the elimination of expanded polyglutamine proteins and leads to preservation of proteasome function. J Biol Chem 278(24):22044–22055. doi:10.1074/jbc.M212235200
Chhangani D, Jana NR, Mishra A (2013) Misfolded proteins recognition strategies of E3 ubiquitin ligases and neurodegenerative diseases. Mol Neurobiol. doi:10.1007/s12035-012-8351-0
Stefani M, Dobson C (2003) Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. J Mol Med (Berlin, Germany) 81(11):678–699. doi:10.1007/s00109-003-0464-5
Bucciantini M, Giannoni E, Chiti F, Baroni F, Formigli L, Zurdo J, Taddei N, Ramponi G, Dobson C, Stefani M (2002) Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416(6880):507–511. doi:10.1038/416507a
Bence NF, Sampat RM, Kopito RR (2001) Impairment of the ubiquitin–proteasome system by protein aggregation. Science 292(5521):1552–1555. doi:10.1126/science.292.5521.1552
Mizushima N, Levine B, Cuervo A, Klionsky D (2008) Autophagy fights disease through cellular self-digestion. Nature 451(7182):1069–1075. doi:10.1038/nature06639
Menzies FM, Moreau K, Rubinsztein DC (2011) Protein misfolding disorders and macroautophagy. Curr Opin Cell Biol 23(2):190–197. doi:10.1016/j.ceb.2010.10.010
Kon M, Cuervo AM (2010) Autophagy: an alternative degradation mechanism for misfolded proteins. John Wiley & Sons, Inc., Hoboken, pp 113–129
Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y (2009) Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol 10(7):458–467. doi:10.1038/nrm2708
Mijaljica D, Prescott M, Devenish R (2011) Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Autophagy 7(7):673–682
Dice J (2007) Chaperone-mediated autophagy. Autophagy 3(4):295–299
Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147(4):728–741. doi:10.1016/j.cell.2011.10.026
Nixon RA (2006) Autophagy in neurodegenerative disease: friend, foe or turncoat? Trends Neurosci 29(9):528–535. doi:10.1016/j.tins.2006.07.003
Mizushima N, Yoshimori T, Ohsumi Y (2011) The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 27:107–132. doi:10.1146/annurev-cellbio-092910-154005
Ragusa MJ, Stanley RE, Hurley JH (2012) Architecture of the atg17 complex as a scaffold for autophagosome biogenesis. Cell 151(7):1501–1512. doi:10.1016/j.cell.2012.11.028
Kraft C, Peter M, Hofmann K (2010) Selective autophagy: ubiquitin-mediated recognition and beyond. Nat Cell Biol 12(9):836–841. doi:10.1038/ncb0910-836
Kirkin V, McEwan D, Novak I, Dikic I (2009) A role for ubiquitin in selective autophagy. Mol Cell 34(3):259–269. doi:10.1016/j.molcel.2009.04.026
Bjørkøy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, Stenmark H, Johansen T (2005) p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 171(4):603–614. doi:10.2307/3658468
Kirkin V, Lamark T, Sou Y-S, Bjørkøy G, Nunn J, Bruun J-A, Shvets E, McEwan D, Clausen T, Wild P, Bilusic I, Theurillat J-P, Øvervatn A, Ishii T, Elazar Z, Komatsu M, Dikic I, Johansen T (2009) A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell 33(4):505–516. doi:10.1016/j.molcel.2009.01.020
Pankiv S, Clausen T, Lamark T, Brech A, Bruun J-A, Outzen H, Øvervatn A, Bjørkøy G, Johansen T (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282(33):24131–24145. doi:10.1074/jbc.M702824200
Chiang HL, Dice JF (1988) Peptide sequences that target proteins for enhanced degradation during serum withdrawal. J Biol Chem 263(14):6797–6805
Cuervo A, Dice J (1996) A receptor for the selective uptake and degradation of proteins by lysosomes. Science (New York, NY) 273(5274):501–503
Schatz G, Dobberstein B (1996) Common principles of protein translocation across membranes. Science (New York, NY) 271(5255):1519–1526
Chirico W, Waters M, Blobel G (1988) 70K heat shock related proteins stimulate protein translocation into microsomes. Nature 332(6167):805–810. doi:10.1038/332805a0
Chiang H, Terlecky S, Plant C, Dice J (1989) A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science (New York, NY) 246(4928):382–385
Nylandsted J, Gyrd-Hansen M, Danielewicz A, Fehrenbacher N, Lademann U, Høyer-Hansen M, Weber E, Multhoff G, Rohde M, Jäättelä M (2004) Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J Exp Med 200(4):425–435. doi:10.1084/jem.20040531
Kirkegaard T, Roth A, Petersen N, Mahalka A, Olsen O, Moilanen I, Zylicz A, Knudsen J, Sandhoff K, Arenz C, Kinnunen P, Nylandsted J, Jäättelä M (2010) Hsp70 stabilizes lysosomes and reverts Niemann–Pick disease-associated lysosomal pathology. Nature 463(7280):549–553. doi:10.1038/nature08710
Qi L, Zhang X-D, Wu J-C, Lin F, Wang J, Difiglia M, Qin Z-H (2012) The role of chaperone-mediated autophagy in huntingtin degradation. PLoS One 7(10): doi:10.1371/journal.pone.0046834
Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441(7095):885–889. doi:10.1038/nature04724
Komatsu M, Waguri S, Chiba T, Murata S, Iwata J-i, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E, Tanaka K (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441(7095):880–884. doi:10.1038/nature04723
Malkus K, Ischiropoulos H (2012) Regional deficiencies in chaperone-mediated autophagy underlie α-synuclein aggregation and neurodegeneration. Neurobiol Dis 46(3):732–744. doi:10.1016/j.nbd.2012.03.017
d’Azzo A, Bongiovanni A, Nastasi T (2005) E3 ubiquitin ligases as regulators of membrane protein trafficking and degradation. Traffic 6(6):429–441. doi:10.1111/j.1600-0854.2005.00294.x
Chakrabarti O, Hegde R (2009) Functional depletion of mahogunin by cytosolically exposed prion protein contributes to neurodegeneration. Cell 137(6):1136–1147. doi:10.1016/j.cell.2009.03.042
Lévy F, Muehlethaler K, Salvi S, Peitrequin A-L, Lindholm C, Cerottini J-C, Rimoldi D (2005) Ubiquitylation of a melanosomal protein by HECT-E3 ligases serves as sorting signal for lysosomal degradation. Mol Biol Cell 16(4):1777–1787. doi:10.1091/mbc.E04-09-0803
Squier TC (2001) Oxidative stress and protein aggregation during biological aging. Exp Gerontol 36(9):1539–1550
Rao RV, Bredesen DE (2004) Misfolded proteins, endoplasmic reticulum stress and neurodegeneration. Curr Opin Cell Biol 16(6):653–662. doi:10.1016/j.ceb.2004.09.012
Malhotra JD, Kaufman RJ (2007) Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal 9(12):2277–2293. doi:10.1089/ars.2007.1782
Sato B, Schulz D, Do P, Hampton R (2009) Misfolded membrane proteins are specifically recognized by the transmembrane domain of the Hrd1p ubiquitin ligase. Mol Cell 34(2):212–222. doi:10.1016/j.molcel.2009.03.010
Mannini B, Cascella R, Zampagni M, van Waarde-Verhagen M, Meehan S, Roodveldt C, Campioni S, Boninsegna M, Penco A, Relini A, Kampinga HH, Dobson CM, Wilson MR, Cecchi C, Chiti F (2012) Molecular mechanisms used by chaperones to reduce the toxicity of aberrant protein oligomers. Proc Natl Acad Sci U S A 109(31):12479–12484. doi:10.1073/pnas.1117799109
Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295(5561):1852–1858. doi:10.1126/science.1068408
Morimoto RI (1998) Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 12(24):3788–3796
Finka A, Mattoo RU, Goloubinoff P (2011) Meta-analysis of heat- and chemically upregulated chaperone genes in plant and human cells. Cell Stress Chaperones 16(1):15–31. doi:10.1007/s12192-010-0216-8
Banerjee Mustafi S, Chakraborty PK, Dey RS, Raha S (2009) Heat stress upregulates chaperone heat shock protein 70 and antioxidant manganese superoxide dismutase through reactive oxygen species (ROS), p38MAPK, and Akt. Cell Stress Chaperones 14(6):579–589. doi:10.1007/s12192-009-0109-x
Bruening W, Roy J, Giasson B, Figlewicz DA, Mushynski WE, Durham HD (1999) Up-regulation of protein chaperones preserves viability of cells expressing toxic Cu/Zn-superoxide dismutase mutants associated with amyotrophic lateral sclerosis. J Neurochem 72(2):693–699
Morimoto RI (2008) Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. Genes Dev 22(11):1427–1438. doi:10.1101/gad.1657108
Goldbaum O, Oppermann M, Handschuh M, Dabir D, Zhang B, Forman MS, Trojanowski JQ, Lee VM, Richter-Landsberg C (2003) Proteasome inhibition stabilizes tau inclusions in oligodendroglial cells that occur after treatment with okadaic acid. J Neurosci 23(26):8872–8880
Ito H, Kamei K, Iwamoto I, Inaguma Y, Garcia-Mata R, Sztul E, Kato K (2002) Inhibition of proteasomes induces accumulation, phosphorylation, and recruitment of HSP27 and alphaB-crystallin to aggresomes. J Biochem 131(4):593–603
Voellmy R, Boellmann F (2007) Chaperone regulation of the heat shock protein response. Adv Exp Med Biol 594:89–99. doi:10.1007/978-0-387-39975-1_9
Henderson B (2010) Integrating the cell stress response: a new view of molecular chaperones as immunological and physiological homeostatic regulators. Cell Biochem Funct 28(1):1–14. doi:10.1002/cbf.1609
Papp E, Nardai G, Soti C, Csermely P (2003) Molecular chaperones, stress proteins and redox homeostasis. Biofactors 17(1–4):249–257
Qian SB, McDonough H, Boellmann F, Cyr DM, Patterson C (2006) CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70. Nature 440(7083):551–555. doi:10.1038/nature04600
Tsuiji H, Iguchi Y, Furuya A, Kataoka A, Hatsuta H, Atsuta N, Tanaka F, Hashizume Y, Akatsu H, Murayama S, Sobue G, Yamanaka K (2012) Spliceosome integrity is defective in the motor neuron diseases ALS and SMA. EMBO Mol Med. doi:10.1002/emmm.201202303
Fernandes R, Ramalho J, Pereira P (2006) Oxidative stress upregulates ubiquitin proteasome pathway in retinal endothelial cells. Mol Vis 12:1526–1535
Imai Y, Soda M, Takahashi R (2000) Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin–protein ligase activity. J Biol Chem 275(46):35661–35664. doi:10.1074/jbc.C000447200
Braten O, Shabek N, Kravtsova-Ivantsiv Y, Ciechanover A (2012) Generation of free ubiquitin chains is up-regulated in stress and facilitated by the HECT domain ubiquitin ligases UFD4 and HUL5. Biochem J 444(3):611–617. doi:10.1042/BJ20111840
Ding WX, Ni HM, Gao W, Yoshimori T, Stolz DB, Ron D, Yin XM (2007) Linking of autophagy to ubiquitin–proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am J Pathol 171(2):513–524. doi:10.2353/ajpath.2007.070188
Bennett EJ, Bence NF, Jayakumar R, Kopito RR (2005) Global impairment of the ubiquitin–proteasome system by nuclear or cytoplasmic protein aggregates precedes inclusion body formation. Mol Cell 17(3):351–365. doi:10.1016/j.molcel.2004.12.021
Cecarini V, Bonfili L, Cuccioloni M, Mozzicafreddo M, Rossi G, Buizza L, Uberti D, Angeletti M, Eleuteri AM (2012) Crosstalk between the ubiquitin–proteasome system and autophagy in a human cellular model of Alzheimer's disease. Biochim Biophys Acta 1822(11):1741–1751. doi:10.1016/j.bbadis.2012.07.015
Ebrahimi-Fakhari D, Cantuti-Castelvetri I, Fan Z, Rockenstein E, Masliah E, Hyman BT, McLean PJ, Unni VK (2011) Distinct roles in vivo for the ubiquitin–proteasome system and the autophagy-lysosomal pathway in the degradation of alpha-synuclein. J Neurosci 31(41):14508–14520. doi:10.1523/JNEUROSCI.1560-11.2011
Gamerdinger M, Kaya AM, Wolfrum U, Clement AM, Behl C (2011) BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins. EMBO Rep 12(2):149–156. doi:10.1038/embor.2010.203
Behl C (2011) BAG3 and friends: co-chaperones in selective autophagy during aging and disease. Autophagy 7(7):795–798. doi:10.4161/auto.7.7.15844
Metcalf DJ, Garcia-Arencibia M, Hochfeld WE, Rubinsztein DC (2010) Autophagy and misfolded proteins in neurodegeneration. Exp Neurol 238(1):22–28. doi:10.1016/j.expneurol.2010.11.003
Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, Shiosaka S, Hammarback JA, Urano F, Imaizumi K (2006) Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 26(24):9220–9231. doi:10.1128/MCB.01453-06
Chen Y, McMillan-Ward E, Kong J, Israels SJ, Gibson SB (2008) Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells. Cell Death Differ 15(1):171–182. doi:10.1038/sj.cdd.4402233
Ge PF, Zhang JZ, Wang XF, Meng FK, Li WC, Luan YX, Ling F, Luo YN (2009) Inhibition of autophagy induced by proteasome inhibition increases cell death in human SHG-44 glioma cells. Acta Pharmacol Sin 30(7):1046–1052. doi:10.1038/aps.2009.71
Liu TT, Hu CH, Tsai CD, Li CW, Lin YF, Wang JY (2010) Heat stroke induces autophagy as a protection mechanism against neurodegeneration in the brain. Shock 34(6):643–648. doi:10.1097/SHK.0b013e3181e761c1
Yorimitsu T, Nair U, Yang Z, Klionsky DJ (2006) Endoplasmic reticulum stress triggers autophagy. J Biol Chem 281(40):30299–30304. doi:10.1074/jbc.M607007200
Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281(5381):1322–1326
Tibbles LA, Woodgett JR (1999) The stress-activated protein kinase pathways. Cell Mol Life Sci 55(10):1230–1254
Konishi H, Matsuzaki H, Tanaka M, Takemura Y, Kuroda S, Ono Y, Kikkawa U (1997) Activation of protein kinase B (Akt/RAC-protein kinase) by cellular stress and its association with heat shock protein Hsp27. FEBS Lett 410(2–3):493–498
Nishiyama Y, Shimada Y, Yokoi T, Kobayashi H, Higuchi T, Eto Y, Ida H, Ohashi T (2012) Akt inactivation induces endoplasmic reticulum stress-independent autophagy in fibroblasts from patients with Pompe disease. Mol Genet Metab 107(3):490–495
Goswami A, Dikshit P, Mishra A, Nukina N, Jana NR (2006) Expression of expanded polyglutamine proteins suppresses the activation of transcription factor NFkappaB. J Biol Chem 281(48):37017–37024. doi:10.1074/jbc.M608095200
Shono T, Ono M, Izumi H, Jimi SI, Matsushima K, Okamoto T, Kohno K, Kuwano M (1996) Involvement of the transcription factor NF-kappaB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. Mol Cell Biol 16(8):4231–4239
Nivon M, Abou-Samra M, Richet E, Guyot B, Arrigo AP, Kretz-Remy C (2012) NF-kappaB regulates protein quality control after heat stress through modulation of the BAG3-HspB8 complex. J Cell Sci 125(Pt 5):1141–1151. doi:10.1242/jcs.091041
Kretz-Remy C, Munsch B, Arrigo AP (2001) NFkappa B-dependent transcriptional activation during heat shock recovery. Thermolability of the NF-kappaB.Ikappa B complex. J Biol Chem 276(47):43723–43733. doi:10.1074/jbc.M010821200
Pahl HL, Baeuerle PA (1996) Activation of NF-kappa B by ER stress requires both Ca2+ and reactive oxygen intermediates as messengers. FEBS Lett 392(2):129–136
Mercurio F, Manning AM (1999) NF-kappaB as a primary regulator of the stress response. Oncogene 18(45):6163–6171. doi:10.1038/sj.onc.1203174
Meusser B, Hirsch C, Jarosch E, Sommer T (2005) ERAD: the long road to destruction. Nat Cell Biol 7(8):766–772. doi:10.1038/ncb0805-766
Lindholm D, Wootz H, Korhonen L (2006) ER stress and neurodegenerative diseases. Cell Death Differ 13(3):385–392. doi:10.1038/sj.cdd.4401778
Sekine Y, Takeda K, Ichijo H (2006) The ASK1-MAP kinase signaling in ER stress and neurodegenerative diseases. Curr Mol Med 6(1):87–97
Watanabe S, Kaneko K, Yamanaka K (2012) Accelerated disease onset with stabilized familial Amyotrophic Lateral Sclerosis (ALS)-linked TDP-43 mutations. J Biol Chem. doi:10.1074/jbc.M112.433615
Nishitoh H, Kadowaki H, Nagai A, Maruyama T, Yokota T, Fukutomi H, Noguchi T, Matsuzawa A, Takeda K, Ichijo H (2008) ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1. Genes Dev 22(11):1451–1464. doi:10.1101/gad.1640108
Atkin JD, Farg MA, Turner BJ, Tomas D, Lysaght JA, Nunan J, Rembach A, Nagley P, Beart PM, Cheema SS, Horne MK (2006) Induction of the unfolded protein response in familial amyotrophic lateral sclerosis and association of protein-disulfide isomerase with superoxide dismutase 1. J Biol Chem 281(40):30152–30165. doi:10.1074/jbc.M603393200
Kikuchi H, Almer G, Yamashita S, Guegan C, Nagai M, Xu Z, Sosunov AA, McKhann GM 2nd, Przedborski S (2006) Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutase-1 in an ALS model. Proc Natl Acad Sci U S A 103(15):6025–6030. doi:10.1073/pnas.0509227103
Patel J, McLeod LE, Vries RG, Flynn A, Wang X, Proud CG (2002) Cellular stresses profoundly inhibit protein synthesis and modulate the states of phosphorylation of multiple translation factors. Eur J Biochem 269(12):3076–3085
Stefani M, Dobson CM (2003) Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. J Mol Med (Berl) 81(11):678–699. doi:10.1007/s00109-003-0464-5
Spriggs KA, Bushell M, Willis AE (2010) Translational regulation of gene expression during conditions of cell stress. Mol Cell 40(2):228–237. doi:10.1016/j.molcel.2010.09.028
Fox S (2012) Lost in translation: misfolded proteins may cause neurodegeneration by inhibiting normal protein production. Mov Disord 27(10):1218
Bahmanyar S, Higgins GA, Goldgaber D, Lewis DA, Morrison JH, Wilson MC, Shankar SK, Gajdusek DC (1987) Localization of amyloid beta protein messenger RNA in brains from patients with Alzheimer's disease. Science 237(4810):77–80
Scheper GC, van der Knaap MS, Proud CG (2007) Translation matters: protein synthesis defects in inherited disease. Nat Rev Genet 8(9):711–723. doi:10.1038/nrg2142
Mishra A, Jana NR (2008) Regulation of turnover of tumor suppressor p53 and cell growth by E6-AP, a ubiquitin protein ligase mutated in Angelman mental retardation syndrome. Cell Mol Life Sci 65(4):656–666. doi:10.1007/s00018-007-7476-1
Mishra A, Godavarthi SK, Jana NR (2009) UBE3A/E6-AP regulates cell proliferation by promoting proteasomal degradation of p27. Neurobiol Dis 36(1):26–34. doi:10.1016/j.nbd.2009.06.010
Novoa I, Zhang Y, Zeng H, Jungreis R, Harding HP, Ron D (2003) Stress-induced gene expression requires programmed recovery from translational repression. EMBO J 22(5):1180–1187. doi:10.1093/emboj/cdg112
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(5):1099–1108
Morimoto RI (1993) Cells in stress: transcriptional activation of heat shock genes. Science 259(5100):1409–1410
Lesley SA, Graziano J, Cho CY, Knuth MW, Klock HE (2002) Gene expression response to misfolded protein as a screen for soluble recombinant protein. Protein Eng 15(2):153–160
Kubota H (2009) Quality control against misfolded proteins in the cytosol: a network for cell survival. J Biochem 146(5):609–616. doi:10.1093/jb/mvp139
Bukau B, Weissman J, Horwich A (2006) Molecular chaperones and protein quality control. Cell 125(3):443–451. doi:10.1016/j.cell.2006.04.014
Schlecht R, Erbse AH, Bukau B, Mayer MP (2011) Mechanics of Hsp70 chaperones enables differential interaction with client proteins. Nat Struct Mol Biol 18(3):345–351. doi:10.1038/nsmb.2006
Albanese V, Frydman J (2002) Where chaperones and nascent polypeptides meet. Nat Struct Biol 9(10):716–718. doi:10.1038/nsb1002-716
Frydman J, Nimmesgern E, Ohtsuka K, Hartl FU (1994) Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones. Nature 370(6485):111–117. doi:10.1038/370111a0
Warrick JM, Chan HY, Gray-Board GL, Chai Y, Paulson HL, Bonini NM (1999) Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat Genet 23(4):425–428. doi:10.1038/70532
Muchowski PJ (2002) Protein misfolding, amyloid formation, and neurodegeneration: a critical role for molecular chaperones? Neuron 35(1):9–12
Forman MS, Lee VM, Trojanowski JQ (2003) 'Unfolding' pathways in neurodegenerative disease. Trends Neurosci 26(8):407–410. doi:10.1016/S0166-2236(03)00197-8
Frydman J (2001) Folding of newly translated proteins in vivo: the role of molecular chaperones. Annu Rev Biochem 70:603–647. doi:10.1146/annurev.biochem.70.1.603
Koplin A, Preissler S, Ilina Y, Koch M, Scior A, Erhardt M, Deuerling E (2010) A dual function for chaperones SSB-RAC and the NAC nascent polypeptide-associated complex on ribosomes. J Cell Biol 189(1):57–68. doi:10.1083/jcb.200910074
Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB, Schwartz SL, DiProspero NA, Knight MA, Schuldiner O, Padmanabhan R, Hild M, Berry DL, Garza D, Hubbert CC, Yao TP, Baehrecke EH, Taylor JP (2007) HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447(7146):859–863. doi:10.1038/nature05853
Nedelsky NB, Todd PK, Taylor JP (2008) Autophagy and the ubiquitin–proteasome system: collaborators in neuroprotection. Biochim Biophys Acta 1782(12):691–699. doi:10.1016/j.bbadis.2008.10.002
Goldberg AL (2003) Protein degradation and protection against misfolded or damaged proteins. Nature 426(6968):895–899. doi:10.1038/nature02263
Kaganovich D, Kopito R, Frydman J (2008) Misfolded proteins partition between two distinct quality control compartments. Nature 454(7208):1088–1095. doi:10.1038/nature07195
Bagola K, Sommer T (2008) Protein quality control: on IPODs and other JUNQ. Curr Biol 18(21):R1019–R1021. doi:10.1016/j.cub.2008.09.036
Seckler R, Jaenicke R (1992) Protein folding and protein refolding. FASEB J 6(8):2545–2552
Wong E, Cuervo AM (2010) Integration of clearance mechanisms: the proteasome and autophagy. Cold Spring Harb Perspect Biol 2(12):a006734. doi:10.1101/cshperspect.a006734
Bucciantini M, Giannoni E, Chiti F, Baroni F, Formigli L, Zurdo J, Taddei N, Ramponi G, Dobson CM, Stefani M (2002) Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 416(6880):507–511. doi:10.1038/416507a
Perisic O, Xiao H, Lis JT (1989) Stable binding of Drosophila heat shock factor to head-to-head and tail-to-tail repeats of a conserved 5 bp recognition unit. Cell 59(5):797–806
Clos J, Rabindran S, Wisniewski J, Wu C (1993) Induction temperature of human heat shock factor is reprogrammed in a Drosophila cell environment. Nature 364(6434):252–255. doi:10.1038/364252a0
Dai Q, Zhang C, Wu Y, McDonough H, Whaley RA, Godfrey V, Li HH, Madamanchi N, Xu W, Neckers L, Cyr D, Patterson C (2003) CHIP activates HSF1 and confers protection against apoptosis and cellular stress. EMBO J 22(20):5446–5458. doi:10.1093/emboj/cdg529
Boellmann F, Guettouche T, Guo Y, Fenna M, Mnayer L, Voellmy R (2004) DAXX interacts with heat shock factor 1 during stress activation and enhances its transcriptional activity. Proc Natl Acad Sci U S A 101(12):4100–4105. doi:10.1073/pnas.0304768101
Biro K, Palhalmi J, Toth AJ, Kukorelli T, Juhasz G (1998) Bimoclomol improves early electrophysiological signs of retinopathy in diabetic rats. Neuroreport 9(9):2029–2033
Polakowski JS, Wegner CD, Cox BF (2002) Bimoclomol elevates heat shock protein 70 and cytoprotects rat neonatal cardiomyocytes. Eur J Pharmacol 435(1):73–77
Lubbers NL, Polakowski JS, Wegner CD, Burke SE, Diaz GJ, Daniell KM, Cox BF (2002) Oral bimoclomol elevates heat shock protein 70 and reduces myocardial infarct size in rats. Eur J Pharmacol 435(1):79–83
Erdo F, Erdo SL (1998) Bimoclomol protects against vascular consequences of experimental subarachnoid hemorrhage in rats. Brain Res Bull 45(2):163–166
Vigh L, Literati PN, Horvath I, Torok Z, Balogh G, Glatz A, Kovacs E, Boros I, Ferdinandy P, Farkas B, Jaszlits L, Jednakovits A, Koranyi L, Maresca B (1997) Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects. Nat Med 3(10):1150–1154
Hargitai J, Lewis H, Boros I, Racz T, Fiser A, Kurucz I, Benjamin I, Vigh L, Penzes Z, Csermely P, Latchman DS (2003) Bimoclomol, a heat shock protein co-inducer, acts by the prolonged activation of heat shock factor-1. Biochem Biophys Res Commun 307(3):689–695
Liu AY, Mathur R, Mei N, Langhammer CG, Babiarz B, Firestein BL (2011) Neuroprotective drug riluzole amplifies the heat shock factor 1 (HSF1)- and glutamate transporter 1 (GLT1)-dependent cytoprotective mechanisms for neuronal survival. J Biol Chem 286(4):2785–2794. doi:10.1074/jbc.M110.158220
Miller RG, Mitchell JD, Moore DH (2007) Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev 3:CD001447. doi:10.1002/14651858.CD001447.pub3
Yang J, Bridges K, Chen KY, Liu AY (2008) Riluzole increases the amount of latent HSF1 for an amplified heat shock response and cytoprotection. PLoS One 3(8):e2864. doi:10.1371/journal.pone.0002864
Lillie SH, Pringle JR (1980) Reserve carbohydrate metabolism in Saccharomyces cerevisiae: responses to nutrient limitation. J Bacteriol 143(3):1384–1394
Singer MA, Lindquist S (1998) Multiple effects of trehalose on protein folding in vitro and in vivo. Mol Cell 1(5):639–648
Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, Doi H, Kurosawa M, Nekooki M, Nukina N (2004) Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med 10(2):148–154. doi:10.1038/nm985
Uversky VN, Li J, Fink AL (2001) Trimethylamine-N-oxide-induced folding of alpha-synuclein. FEBS Lett 509(1):31–35
Wei H, Kim SJ, Zhang Z, Tsai PC, Wisniewski KE, Mukherjee AB (2008) ER and oxidative stresses are common mediators of apoptosis in both neurodegenerative and non-neurodegenerative lysosomal storage disorders and are alleviated by chemical chaperones. Hum Mol Genet 17(4):469–477. doi:10.1093/hmg/ddm324
Sato S, Ward CL, Krouse ME, Wine JJ, Kopito RR (1996) Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation. J Biol Chem 271(2):635–638
Mishra R, Bhat R, Seckler R (2007) Chemical chaperone-mediated protein folding: stabilization of P22 tailspike folding intermediates by glycerol. Biol Chem 388(8):797–804. doi:10.1515/BC.2007.096
Yoshida H, Yoshizawa T, Shibasaki F, Shoji S, Kanazawa I (2002) Chemical chaperones reduce aggregate formation and cell death caused by the truncated Machado–Joseph disease gene product with an expanded polyglutamine stretch. Neurobiol Dis 10(2):88–99
Wong E, Cuervo AM (2010) Autophagy gone awry in neurodegenerative diseases. Nat Neurosci 13(7):805–811. doi:10.1038/nn.2575
Bedford L, Hay D, Devoy A, Paine S, Powe DG, Seth R, Gray T, Topham I, Fone K, Rezvani N, Mee M, Soane T, Layfield R, Sheppard PW, Ebendal T, Usoskin D, Lowe J, Mayer RJ (2008) Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies. J Neurosci 28(33):8189–8198. doi:10.1523/JNEUROSCI.2218-08.2008
Egeler EL, Urner LM, Rakhit R, Liu CW, Wandless TJ (2011) Ligand-switchable substrates for a ubiquitin–proteasome system. J Biol Chem 286(36):31328–31336. doi:10.1074/jbc.M111.264101
Banaszynski LA, Chen LC, Maynard-Smith LA, Ooi AG, Wandless TJ (2006) A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules. Cell 126(5):995–1004. doi:10.1016/j.cell.2006.07.025
Ochocka AM, Kampanis P, Nicol S, Allende-Vega N, Cox M, Marcar L, Milne D, Fuller-Pace F, Meek D (2009) FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and activation of p53. FEBS Lett 583(4):621–626. doi:10.1016/j.febslet.2009.01.009
Gestwicki JE, Crabtree GR, Graef IA (2004) Harnessing chaperones to generate small-molecule inhibitors of amyloid beta aggregation. Science 306(5697):865–869. doi:10.1126/science.1101262
Zhou P, Bogacki R, McReynolds L, Howley PM (2000) Harnessing the ubiquitination machinery to target the degradation of specific cellular proteins. Mol Cell 6(3):751–756
Zhang D, Baek SH, Ho A, Lee H, Jeong YS, Kim K (2004) Targeted degradation of proteins by small molecules: a novel tool for functional proteomics. Comb Chem High Throughput Screen 7(7):689–697
Sakamoto KM (2005) Chimeric molecules to target proteins for ubiquitination and degradation. Methods Enzymol 399:833–847. doi:10.1016/S0076-6879(05)99054-X
Tang YQ, Han BM, Yao XQ, Hong Y, Wang Y, Zhao FJ, Yu SQ, Sun XW, Xia SJ (2009) Chimeric molecules facilitate the degradation of androgen receptors and repress the growth of LNCaP cells. Asian J Androl 11(1):119–126. doi:10.1038/aja.2008.26
Sakamoto KM, Kim KB, Kumagai A, Mercurio F, Crews CM, Deshaies RJ (2001) Protacs: chimeric molecules that target proteins to the Skp1–Cullin-F box complex for ubiquitination and degradation. Proc Natl Acad Sci U S A 98(15):8554–8559. doi:10.1073/pnas.141230798
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 beta accumulation in mice. J Clin Invest 118(6):2190–2199. doi:10.1172/JCI33585
Mizushima N, Ohsumi Y, Yoshimori T (2002) Autophagosome formation in mammalian cells. Cell Struct Funct 27(6):421–429
Harris CD, Ermak G, Davies KJ (2007) RCAN1-1L is overexpressed in neurons of Alzheimer's disease patients. FEBS J 274(7):1715–1724. doi:10.1111/j.1742-4658.2007.05717.x
Liu H, Wang P, Song W, Sun X (2009) Degradation of regulator of calcineurin 1 (RCAN1) is mediated by both chaperone-mediated autophagy and ubiquitin proteasome pathways. FASEB J 23(10):3383–3392. doi:10.1096/fj.09-134296
Nalepa G, Rolfe M, Harper JW (2006) Drug discovery in the ubiquitin–proteasome system. Nat Rev Drug Discov 5(7):596–613. doi:10.1038/nrd2056
Ringseis R, Keller J, Lukas I, Spielmann J, Most E, Couturier A, Konig B, Hirche F, Stangl GI, Wen G, Eder K (2013) Treatment with pharmacological PPARalpha agonists stimulates the ubiquitin proteasome pathway and myofibrillar protein breakdown in skeletal muscle of rodents. Biochim Biophys Acta 1830(1):2105–2117. doi:10.1016/j.bbagen.2012.09.024
Liu J, Zheng H, Tang M, Ryu YC, Wang X (2008) A therapeutic dose of doxorubicin activates ubiquitin-proteasome system-mediated proteolysis by acting on both the ubiquitination apparatus and proteasome. Am J Physiol Heart Circ Physiol 295(6):H2541–H2550. doi:10.1152/ajpheart.01052.2008
Jin S, White E (2008) Tumor suppression by autophagy through the management of metabolic stress. Autophagy 4(5):563–566
Beljanski V, Knaak C, Smith CD (2010) A novel sphingosine kinase inhibitor induces autophagy in tumor cells. J Pharmacol Exp Ther 333(2):454–464. doi:10.1124/jpet.109.163337
Menzies FM, Huebener J, Renna M, Bonin M, Riess O, Rubinsztein DC (2010) Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3. Brain 133(Pt 1):93–104. doi:10.1093/brain/awp292
McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P, Jansen K, Delucia M, Lin WL, Dolios G, Wang R, Eckman CB, Dickson DW, Hutton M, Hardy J, Golde T (2005) Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47(2):191–199. doi:10.1016/j.neuron.2005.06.030
Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D, Richardson A, Strong R, Galvan V (2010) Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS One 5(4):e9979. doi:10.1371/journal.pone.0009979
Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460(7253):392–395. doi:10.1038/nature08221
Kettern N, Dreiseidler M, Tawo R, Hohfeld J (2010) Chaperone-assisted degradation: multiple paths to destruction. Biol Chem 391(5):481–489. doi:10.1515/BC.2010.058
Mishra A, Godavarthi SK, Maheshwari M, Goswami A, Jana NR (2009) The ubiquitin ligase E6-AP is induced and recruited to aggresomes in response to proteasome inhibition and may be involved in the ubiquitination of Hsp70-bound misfolded proteins. J Biol Chem 284(16):10537–10545. doi:10.1074/jbc.M806804200
Murata S, Minami Y, Minami M, Chiba T, Tanaka K (2001) CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Rep 2(12):1133–1138. doi:10.1093/embo-reports/kve246
Murata S, Chiba T, Tanaka K (2003) CHIP: a quality-control E3 ligase collaborating with molecular chaperones. Int J Biochem Cell Biol 35(5):572–578
Iwata A, Christianson JC, Bucci M, Ellerby LM, Nukina N, Forno LS, Kopito RR (2005) Increased susceptibility of cytoplasmic over nuclear polyglutamine aggregates to autophagic degradation. Proc Natl Acad Sci U S A 102(37):13135–13140. doi:10.1073/pnas.0505801102
Arndt V, Dick N, Tawo R, Dreiseidler M, Wenzel D, Hesse M, Furst DO, Saftig P, Saint R, Fleischmann BK, Hoch M, Hohfeld J (2010) Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol 20(2):143–148. doi:10.1016/j.cub.2009.11.022
Acknowledgments
This work was supported by Department of Biotechnology, Government of India. A.M. was supported by a Ramalinganswami fellowship from the Department of Biotechnology, Government of India. The authors thank Mr. Bharat Pareek and Mr. Rahul Sathya Babu for their support and management during manuscript preparation.
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Chhangani, D., Mishra, A. Protein Quality Control System in Neurodegeneration: A Healing Company Hard to Beat but Failure is Fatal. Mol Neurobiol 48, 141–156 (2013). https://doi.org/10.1007/s12035-013-8411-0
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DOI: https://doi.org/10.1007/s12035-013-8411-0