Skip to main content
Log in

Peroxisomal dysfunction in neurodegenerative diseases

  • Review
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Peroxisomes and their (patho-)physiological importance in heath and disease have attracted increasing interest during last few decades. Together with mitochondria, peroxisomes comprise key metabolic platforms for oxidation of various fatty acids and redox regulation. In addition, peroxisomes contribute to bile acid, cholesterol, and plasmalogen biosynthesis. The importance of functional peroxisomes for cellular metabolism is demonstrated by the marked brain and systemic organ abnormalities occuring in peroxisome biogenesis disorders and peroxisomal enzyme deficiencies. Current evidences indicate that peroxisomal function is declined with aging, with peroxisomal dysfunction being linked to early onset of multiple age-related diseases including neurodegenerative diseases. Herein, we review recent progress toward understanding the physiological roles and pathological implications of peroxisomal dysfunctions, focusing on neurodegenerative disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Abdel-Khalik J, Yutuc E, Crick PJ, Gustafsson JA, Warner M, Roman G, Talbot K, Gray E, Griffiths WJ, Turner MR, Wang Y (2017) Defective cholesterol metabolism in amyotrophic lateral sclerosis. J Lipid Res 58:267–278

    Article  CAS  PubMed  Google Scholar 

  • Agrawal G, Subramani S (2016) De novo peroxisome biogenesis: evolving concepts and conundrums. Biochem Biophys Acta 1863:892–901

    Article  CAS  PubMed  Google Scholar 

  • Amaral A, Castillo J, Estanyol JM, Ballesca JL, Ramalho-Santos J, Oliva R (2013) Human sperm tail proteome suggests new endogenous metabolic pathways. Mol Cell Proteom 12:330–342

    Article  CAS  Google Scholar 

  • Anding AL, Baehrecke EH (2017) Cleaning house: selective autophagy of organelles. Dev Cell 41:10–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Antonenkov VD, Grunau S, Ohlmeier S, Hiltunen JK (2010) Peroxisomes are oxidative organelles. Antioxid Redox Signal 13:525–537

    Article  CAS  PubMed  Google Scholar 

  • Astarita G, Jung KM, Berchtold NC, Nguyen VQ, Gillen DL, Head E, Cotman CW, Piomelli D (2010) Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer’s disease. PLoS ONE 5:e12538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aubourg P, Wanders R (2013) Peroxisomal disorders. Handb Clin Neurol 113:1593–1609

    Article  PubMed  Google Scholar 

  • Barberger-Gateau P, Letenneur L, Deschamps V, Peres K, Dartigues JF, Renaud S (2002) Fish, meat, and risk of dementia: cohort study. BMJ (Clin Res ed.) 325:932–933

    Article  Google Scholar 

  • Bar-On P, Crews L, Koob AO, Mizuno H, Adame A, Spencer B, Masliah E (2008) Statins reduce neuronal alpha-synuclein aggregation in in vitro models of Parkinson’s disease. J Neurochem 105:1656–1667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bascoul-Colombo C, Guschina IA, Maskrey BH, Good M, O’Donnell VB, Harwood JL (2016) Dietary DHA supplementation causes selective changes in phospholipids from different brain regions in both wild type mice and the Tg2576 mouse model of Alzheimer’s disease. Biochem Biophys Acta 1861:524–537

    CAS  PubMed  Google Scholar 

  • Beel AJ, Sakakura M, Barrett PJ, Sanders CR (2010) Direct binding of cholesterol to the amyloid precursor protein: an important interaction in lipid-Alzheimer’s disease relationships? Biochem Biophys Acta 1801:975–982

    CAS  PubMed  Google Scholar 

  • Belkouch M, Hachem M, Elgot A, Van Lo A, Picq M, Guichardant M, Lagarde M, Bernoud-Hubac N (2016) The pleiotropic effects of omega-3 docosahexaenoic acid on the hallmarks of Alzheimer’s disease. J Nutr Biochem 38:1–11

    Article  CAS  PubMed  Google Scholar 

  • Blandini F, Armentero MT (2012) Animal models of Parkinson’s disease. FEBS J 279:1156–1166

    Article  CAS  PubMed  Google Scholar 

  • Bolner A, Micciolo R, Bosello O, Nordera GP (2016) A panel of oxidative stress markers in Parkinson’s disease. Clin Lab 62:105–112

    Article  CAS  PubMed  Google Scholar 

  • Bonekamp NA, Volkl A, Fahimi HD, Schrader M (2009) Reactive oxygen species and peroxisomes: struggling for balance. BioFactors (Oxford, England) 35:346–355

    Article  CAS  Google Scholar 

  • Bourre JM (2004) Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing. J Nutr Health Aging 8:163–174

    CAS  PubMed  Google Scholar 

  • Boveris A, Oshino N, Chance B (1972) The cellular production of hydrogen peroxide. Biochem J 128:617–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bowers WE (1998) Christian de Duve and the discovery of lysosomes and peroxisomes. Trends Cell Biol 8:330–333

    Article  CAS  PubMed  Google Scholar 

  • Braverman NE, Moser AB (2012) Functions of plasmalogen lipids in health and disease. Biochem Biophys Acta 1822:1442–1452

    CAS  PubMed  Google Scholar 

  • Braverman NE, D’Agostino MD, Maclean GE (2013) Peroxisome biogenesis disorders: biological, clinical and pathophysiological perspectives. Dev Disabil Res Rev 17:187–196

    Article  PubMed  Google Scholar 

  • Breidert T, Callebert J, Heneka MT, Landreth G, Launay JM, Hirsch EC (2002) Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson’s disease. J Neurochem 82:615–624

    Article  CAS  PubMed  Google Scholar 

  • Brites P, Waterham HR, Wanders RJ (2004) Functions and biosynthesis of plasmalogens in health and disease. Biochem Biophys Acta 1636:219–231

    CAS  PubMed  Google Scholar 

  • Calder PC (2006) n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83:1505s–1519s

    Article  CAS  PubMed  Google Scholar 

  • Calderon F, Kim HY (2004) Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem 90:979–988

    Article  CAS  PubMed  Google Scholar 

  • Carrillo-Mora P, Luna R, Colin-Barenque L (2014) Amyloid beta: multiple mechanisms of toxicity and only some protective effects? Oxid Med Cell Longev 2014:795375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cerri S, Blandini F (2018) Role of autophagy in Parkinson’s disease. Curr Med Chem. https://doi.org/10.2174/0929867325666180226094351

    Article  Google Scholar 

  • Chaturvedi RK, Beal MF (2008) PPAR: a therapeutic target in Parkinson’s disease. J Neurochem 106:506–518

    Article  CAS  PubMed  Google Scholar 

  • Cheng D, Kim WS, Garner B (2008) Regulation of alpha-synuclein expression by liver X receptor ligands in vitro. NeuroReport 19:1685–1689

    Article  CAS  PubMed  Google Scholar 

  • Cheng D, Jenner AM, Shui G, Cheong WF, Mitchell TW, Nealon JR, Kim WS, McCann H, Wenk MR, Halliday GM, Garner B (2011) Lipid pathway alterations in Parkinson’s disease primary visual cortex. PLoS ONE 6:e17299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen-Plotkin AS, Albin R, Alcalay R, Babcock D, Bajaj V, Bowman D, Buko A, Cedarbaum J, Chelsky D, Cookson, Dawson TM, Dewey R, Foroud T, Frasier M, German D, Gwinn K, Huang X, Kopil C, Kremer T, Lasch S, Marek K, Marto JA, Merchant K, Mollenhauer B, Naito A, Potashkin J, Reimer A, Rosenthal LS, Saunders-Pullman R, Scherzer CR, Sherer T, Singleton A, Sutherland M, Thiele I, van der Brug M, Van Keuren-Jensen K, Vaillancourt D, Walt D, West A, Zhang J (2018) Finding useful biomarkers for Parkinson’s disease. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aam6003

    Article  PubMed  PubMed Central  Google Scholar 

  • Cherubini A, Andres-Lacueva C, Martin A, Lauretani F, Iorio AD, Bartali B, Corsi A, Bandinelli S, Mattson MP, Ferrucci L (2007) Low plasma N-3 fatty acids and dementia in older persons: the InCHIANTI study. J Gerontol Series A 62:1120–1126

    Article  Google Scholar 

  • Chinetti G, Fruchart JC, Staels B (2000) Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res 49:497–505

    Article  CAS  PubMed  Google Scholar 

  • Cho DH, Kim YS, Jo DS, Choe SK, Jo EK (2018) Pexophagy: molecular mechanisms and implications for health and diseases. Mol Cells 41:55–64

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chu BB, Liao YC, Qi W, Xie C, Du X, Wang J, Yang H, Miao HH, Li BL, Song BL (2015) Cholesterol transport through lysosome-peroxisome membrane contacts. Cell 161:291–306

    Article  CAS  PubMed  Google Scholar 

  • Cipolla CM, Lodhi IJ (2017) Peroxisomal dysfunction in age-related diseases. Trends Endocrinol Metabol 28:297–308

    Article  CAS  Google Scholar 

  • Congdon EE, Sigurdsson EM (2018) Tau-targeting therapies for Alzheimer disease. Nat Rev Neurol 14:399–415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conquer JA, Tierney MC, Zecevic J, Bettger WJ, Fisher RH (2000) Fatty acid analysis of blood plasma of patients with Alzheimer’s disease, other types of dementia, and cognitive impairment. Lipids 35:1305–1312

    Article  CAS  PubMed  Google Scholar 

  • Cordeiro RM (2014) Reactive oxygen species at phospholipid bilayers: distribution, mobility and permeation. Biochem Biophys Acta 1838:438–444

    Article  CAS  PubMed  Google Scholar 

  • Costello JL, Castro IG, Hacker C, Schrader TA, Metz J, Zeuschner D, Azadi AS, Godinho LF, Costina V, Findeisen P, Manner A, Islinger M, Schrader M (2017) ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER. J Cell Biol 216:331–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crane DI (2014) Revisiting the neuropathogenesis of Zellweger syndrome. Neurochem Int 69:1–8

    Article  CAS  PubMed  Google Scholar 

  • Deb R, Nagotu S (2017) Versatility of peroxisomes: an evolving concept. Tissue Cell 49:209–226

    Article  CAS  PubMed  Google Scholar 

  • Deng BQ, Luo Y, Kang X, Li CB, Morisseau C, Yang J, Lee KSS, Huang J, Hu DY, Wu MY, Peng A, Hammock BD, Liu JY (2017) Epoxide metabolites of arachidonate and docosahexaenoate function conversely in acute kidney injury involved in GSK3beta signaling. Proc Natl Acad Sci USA 114:12608–12613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deori NM, Kale A, Maurya PK, Nagotu S (2018) Peroxisomes: role in cellular ageing and age related disorders. Biogerontology 19:303–324

    Article  CAS  PubMed  Google Scholar 

  • Di Cara F, Sheshachalam A, Braverman NE, Rachubinski RA, Simmonds AJ (2017) Peroxisome-mediated metabolism is required for immune response to microbial infection. Immunity 47:93–106.e107

    Article  CAS  PubMed  Google Scholar 

  • Di Paolo G, Kim TW (2011) Linking lipids to Alzheimer’s disease: cholesterol and beyond. Nat Rev Neurosci 12:284–296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dias V, Junn E, Mouradian MM (2013) The role of oxidative stress in Parkinson’s disease. J Parkinson’s Dis 3:461–491

    CAS  Google Scholar 

  • Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C, Shum B, Hacohen N, Chen ZJ, Whelan SP, Fransen M, Nibert ML, Superti-Furga G, Kagan JC (2010) Peroxisomes are signaling platforms for antiviral innate immunity. Cell 141:668–681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doria M, Maugest L, Moreau T, Lizard G, Vejux A (2016) Contribution of cholesterol and oxysterols to the pathophysiology of Parkinson’s disease. Free Radic Biol Med 101:393–400

    Article  CAS  PubMed  Google Scholar 

  • Dragonas C, Bertsch T, Sieber CC, Brosche T (2009) Plasmalogens as a marker of elevated systemic oxidative stress in Parkinson’s disease. Clin Chem Lab Med 47:894–897

    Article  CAS  PubMed  Google Scholar 

  • Du J, Zhang L, Liu S, Zhang C, Huang X, Li J, Zhao N, Wang Z (2009) PPARgamma transcriptionally regulates the expression of insulin-degrading enzyme in primary neurons. Biochem Biophys Res Commun 383:485–490

    Article  CAS  PubMed  Google Scholar 

  • Du Y, Wen Y, Guo X, Hao J, Wang W, He A, Fan Q, Li P, Liu L, Liang X, Zhang F (2018) A genome-wide expression association analysis identifies genes and pathways associated with amyotrophic lateral sclerosis. Cell Mol Neurobiol 38:635–639

    Article  CAS  PubMed  Google Scholar 

  • Dubois V, Eeckhoute J, Lefebvre P, Staels B (2017) Distinct but complementary contributions of PPAR isotypes to energy homeostasis. J Clin Investig 127:1202–1214

    Article  PubMed  PubMed Central  Google Scholar 

  • Fabelo N, Martin V, Santpere G, Marin R, Torrent L, Ferrer I, Diaz M (2011) Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson’s disease and incidental Parkinson’s disease. Mol Medicine (Cambridge, Mass.) 17:1107–1118

    CAS  Google Scholar 

  • Facciotti F, Ramanjaneyulu GS, Lepore M, Sansano S, Cavallari M, Kistowska M, Forss-Petter S, Ni G, Colone A, Singhal A, Berger J, Xia C, Mori L, De Libero G (2012) Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus. Nat Immunol 13:474–480

    Article  CAS  PubMed  Google Scholar 

  • Fan J, Li X, Issop L, Culty M, Papadopoulos V (2016) ACBD2/ECI2-mediated peroxisome-mitochondria interactions in leydig cell steroid biosynthesis. Mol Endocrinol (Baltimore, Md.) 30:763–782

    Article  CAS  Google Scholar 

  • Fantini J, Carlus D, Yahi N (2011) The fusogenic tilted peptide (67-78) of alpha-synuclein is a cholesterol binding domain. Biochem Biophys Acta 1808:2343–2351

    Article  CAS  PubMed  Google Scholar 

  • Farr RL, Lismont C, Terlecky SR, Fransen M (2016) Peroxisome biogenesis in mammalian cells: the impact of genes and environment. Biochem Biophys Acta 1863:1049–1060

    Article  CAS  PubMed  Google Scholar 

  • Faust PL, Kovacs WJ (2014) Cholesterol biosynthesis and ER stress in peroxisome deficiency. Biochimie 98:75–85

    Article  CAS  PubMed  Google Scholar 

  • Ferdinandusse S, Denis S, Faust PL, Wanders RJ (2009) Bile acids: the role of peroxisomes. J Lipid Res 50:2139–2147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferdinandusse S, Jimenez-Sanchez G, Koster J, Denis S, Van Roermund CW, Silva-Zolezzi I, Moser AB, Visser WF, Gulluoglu M, Durmaz O, Demirkol M, Waterham HR, Gokcay G, Wanders RJ, Valle D (2015) A novel bile acid biosynthesis defect due to a deficiency of peroxisomal ABCD3. Hum Mol Genet 24:361–370

    Article  CAS  PubMed  Google Scholar 

  • Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247

    Article  CAS  PubMed  Google Scholar 

  • Fox MA, Nieuwesteeg MA, Willson JA, Cepeda M, Damjanovski S (2014) Knockdown of Pex11beta reveals its pivotal role in regulating peroxisomal genes, numbers, and ROS levels in Xenopus laevis A6 cells. In Vitro Cell Dev Biol Anim 50:340–349

    Article  CAS  PubMed  Google Scholar 

  • Fransen M, Nordgren M, Wang B, Apanasets O (2012) Role of peroxisomes in ROS/RNS-metabolism: implications for human disease. Biochem Biophys Acta 1822:1363–1373

    CAS  PubMed  Google Scholar 

  • Fransen M, Lismont C, Walton P (2017) The peroxisome-mitochondria connection: how and why? Int J Mol Sci 18(6):1126

    Article  CAS  PubMed Central  Google Scholar 

  • Frieden C, Garai K (2012) Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer’s disease. Proc Natl Acad Sci USA 109:8913–8918

    Article  PubMed  PubMed Central  Google Scholar 

  • Giacobini E, Gold G (2013) Alzheimer disease therapy–moving from amyloid-beta to tau. Nat Rev Neurol 9:677–686

    Article  CAS  PubMed  Google Scholar 

  • Ginsberg L, Rafique S, Xuereb JH, Rapoport SI, Gershfeld NL (1995) Disease and anatomic specificity of ethanolamine plasmalogen deficiency in Alzheimer’s disease brain. Brain Res 698:223–226

    Article  CAS  PubMed  Google Scholar 

  • Graham WV, Bonito-Oliva A, Sakmar TP (2017) Update on Alzheimer’s disease therapy and prevention strategies. Annu Rev Med 68:413–430

    Article  CAS  PubMed  Google Scholar 

  • Gray E, Rice C, Hares K, Redondo J, Kemp K, Williams M, Brown A, Scolding N, Wilkins A (2014) Reductions in neuronal peroxisomes in multiple sclerosis grey matter. Mult Scler (Houndmills, Basingstoke, England) 20:651–659

    Article  Google Scholar 

  • Green KN, Martinez-Coria H, Khashwji H, Hall EB, Yurko-Mauro KA, Ellis L, LaFerla FM (2007) Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-beta and tau pathology via a mechanism involving presenilin 1 levels. J Neurosci 27:4385–4395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grimm MO, Grimm HS, Tomic I, Beyreuther K, Hartmann T, Bergmann C (2008) Independent inhibition of Alzheimer disease beta- and gamma-secretase cleavage by lowered cholesterol levels. J Biol Chem 283:11302–11311

    Article  CAS  PubMed  Google Scholar 

  • Gudala K, Bansal D, Muthyala H (2013) Role of serum cholesterol in Parkinson’s disease: a meta-analysis of evidence. J Parkinson’s Dis 3:363–370

    CAS  Google Scholar 

  • Guimaraes SC, Schuster M, Bielska E, Dagdas G, Kilaru S, Meadows BR, Schrader M, Steinberg G (2015) Peroxisomes, lipid droplets, and endoplasmic reticulum “hitchhike” on motile early endosomes. J Cell Biol 211:945–954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo X, Song W, Chen K, Chen X, Zheng Z, Cao B, Huang R, Zhao B, Wu Y, Shang HF (2015) The serum lipid profile of Parkinson’s disease patients: a study from China. Int J Neurosci 125:838–844

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto M, Shahdat HM, Katakura M, Tanabe Y, Gamoh S, Miwa K, Shimada T, Shido O (2009) Effects of docosahexaenoic acid on in vitro amyloid beta peptide 25-35 fibrillation. Biochem Biophys Acta 1791:289–296

    CAS  PubMed  Google Scholar 

  • Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, Perry VH, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, Garaschuk O, Boddeke E, Dinarello CA, Breitner JC, Cole GM, Golenbock DT, Kummer MP (2015) Neuroinflammation in Alzheimer’s disease. Lancet Neurol 14:388–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hernandez DG, Reed X, Singleton AB (2016) Genetics in Parkinson disease: mendelian versus non-mendelian inheritance. J Neurochem 139(Suppl 1):59–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hiltunen JK, Mursula AM, Rottensteiner H, Wierenga RK, Kastaniotis AJ, Gurvitz A (2003) The biochemistry of peroxisomal beta-oxidation in the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev 27:35–64

    Article  CAS  PubMed  Google Scholar 

  • Hoefler G, Paschke E, Hoefler S, Moser AB, Moser HW (1991) Photosensitized killing of cultured fibroblasts from patients with peroxisomal disorders due to pyrene fatty acid-mediated ultraviolet damage. J Clin Investig 88:1873–1879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hohn A, Grune T (2013) Lipofuscin: formation, effects and role of macroautophagy. Redox Biol 1:140–144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hooijmans CR, Van der Zee CE, Dederen PJ, Brouwer KM, Reijmer YD, van Groen T, Broersen LM, Lutjohann D, Heerschap A, Kiliaan AJ (2009) DHA and cholesterol containing diets influence Alzheimer-like pathology, cognition and cerebral vasculature in APPswe/PS1dE9 mice. Neurobiol Dis 33:482–498

    Article  CAS  PubMed  Google Scholar 

  • Hossain S, Hashimoto M, Katakura M, Miwa K, Shimada T, Shido O (2009) Mechanism of docosahexaenoic acid-induced inhibition of in vitro Abeta1-42 fibrillation and Abeta1-42-induced toxicity in SH-S5Y5 cells. J Neurochem 111:568–579

    Article  CAS  PubMed  Google Scholar 

  • Hu J, Baker A, Bartel B, Linka N, Mullen RT, Reumann S, Zolman BK (2012) Plant peroxisomes: biogenesis and function. Plant Cell 24:2279–2303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hua R, Cheng D, Coyaud E, Freeman S, Di Pietro E, Wang Y, Vissa A, Yip CM, Fairn GD, Braverman N, Brumell JH, Trimble WS, Raught B, Kim PK (2017) VAPs and ACBD5 tether peroxisomes to the ER for peroxisome maintenance and lipid homeostasis. J Cell Biol 216:367–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hwang O (2013) Role of oxidative stress in Parkinson’s disease. Exp Neurobiol 22:11–17

    Article  PubMed  PubMed Central  Google Scholar 

  • Hwang I, Lee J, Huh JY, Park J, Lee HB, Ho YS, Ha H (2012) Catalase deficiency accelerates diabetic renal injury through peroxisomal dysfunction. Diabetes 61:728–738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Islinger M, Cardoso MJ, Schrader M (2010) Be different–the diversity of peroxisomes in the animal kingdom. Biochem Biophys Acta 1803:881–897

    Article  CAS  PubMed  Google Scholar 

  • Islinger M, Voelkl A, Fahimi HD, Schrader M (2018) The peroxisome: an update on mysteries 2.0. Histochem Cell Biol 150:443–471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Issemann I, Green S (1990) Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347:645–650

    Article  CAS  PubMed  Google Scholar 

  • Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53(Suppl 3):S26–S36 discussion S36-28

    Article  CAS  PubMed  Google Scholar 

  • Jenner P, Olanow CW (1996) Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 47:S161–170

    Article  CAS  PubMed  Google Scholar 

  • Jiang T, Sun Q, Chen S (2016) Oxidative stress: a major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson’s disease and Alzheimer’s disease. Prog Neurobiol 147:1–19

    Article  CAS  PubMed  Google Scholar 

  • Kalmijn S, Launer LJ, Ott A, Witteman JC, Hofman A, Breteler MM (1997) Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol 42:776–782

    Article  CAS  PubMed  Google Scholar 

  • Kamat PK, Kalani A, Rai S, Swarnkar S, Tota S, Nath C, Tyagi N (2016) Mechanism of oxidative stress and synapse dysfunction in the pathogenesis of Alzheimer’s disease: understanding the therapeutics strategies. Mol Neurobiol 53:648–661

    Article  CAS  PubMed  Google Scholar 

  • Kim JY, Jang A, Reddy R, Yoon WH, Jankowsky JL (2016) Neuronal overexpression of human VAPB slows motor impairment and neuromuscular denervation in a mouse model of ALS. Hum Mol Genet 25:4661–4673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koch J, Pranjic K, Huber A, Ellinger A, Hartig A, Kragler F, Brocard C (2010) PEX11 family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance. J Cell Sci 123:3389–3400

    Article  CAS  PubMed  Google Scholar 

  • Koob AO, Ubhi K, Paulsson JF, Kelly J, Rockenstein E, Mante M, Adame A, Masliah E (2010) Lovastatin ameliorates alpha-synuclein accumulation and oxidation in transgenic mouse models of alpha-synucleinopathies. Exp Neurol 221:267–274

    Article  CAS  PubMed  Google Scholar 

  • Kou J, Kovacs GG, Hoftberger R, Kulik W, Brodde A, Forss-Petter S, Honigschnabl S, Gleiss A, Brugger B, Wanders R, Just W, Budka H, Jungwirth S, Fischer P, Berger J (2011) Peroxisomal alterations in Alzheimer’s disease. Acta Neuropathol 122:271–283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kovacs WJ, Tape KN, Shackelford JE, Duan X, Kasumov T, Kelleher JK, Brunengraber H, Krisans SK (2007) Localization of the pre-squalene segment of the isoprenoid biosynthetic pathway in mammalian peroxisomes. Histochem Cell Biol 127:273–290

    Article  CAS  PubMed  Google Scholar 

  • LaFerla FM, Green KN, Oddo S (2007) Intracellular amyloid-beta in Alzheimer’s disease. Nat Rev Neurosci 8:499–509

    Article  CAS  PubMed  Google Scholar 

  • Landreth G (2007) Therapeutic use of agonists of the nuclear receptor PPARgamma in Alzheimer’s disease. Curr Alzheimer Res 4:159–164

    Article  CAS  PubMed  Google Scholar 

  • Lang A, John Peter AT, Kornmann B (2015) ER-mitochondria contact sites in yeast: beyond the myths of ERMES. Curr Opin Cell Biol 35:7–12

    Article  CAS  PubMed  Google Scholar 

  • Legakis JE, Koepke JI, Jedeszko C, Barlaskar F, Terlecky LJ, Edwards HJ, Walton PA, Terlecky SR (2002) Peroxisome senescence in human fibroblasts. Mol Biol Cell 13:4243–4255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim SY, Suzuki H (2000) Intakes of dietary docosahexaenoic acid ethyl ester and egg phosphatidylcholine improve maze-learning ability in young and old mice. J Nutr 130:1629–1632

    Article  CAS  PubMed  Google Scholar 

  • Lizard G, Rouaud O, Demarquoy J, Cherkaoui-Malki M, Iuliano L (2012) Potential roles of peroxisomes in Alzheimer’s disease and in dementia of the Alzheimer’s type. J Alzheimer’s Dis 29:241–254

    Article  CAS  Google Scholar 

  • Lodhi IJ, Wei X, Yin L, Feng C, Adak S, Abou-Ezzi G, Hsu FF, Link DC, Semenkovich CF (2015) Peroxisomal lipid synthesis regulates inflammation by sustaining neutrophil membrane phospholipid composition and viability. Cell Metab 21:51–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG (2005) A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Investig 115:2774–2783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, Chen PP, Hudspeth B, Chen C, Zhao Y, Vinters HV, Frautschy SA, Cole GM (2009) Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J Neurosci 29:9078–9089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marchetti DP, Donida B, Jacques CE, Deon M, Hauschild TC, Koehler-Santos P, de Moura Coelho D, Coitinho AS, Jardim LB, Vargas CR (2018) Inflammatory profile in X-linked adrenoleukodystrophy patients: understanding disease progression. J Cell Biochem 119:1223–1233

    Article  CAS  PubMed  Google Scholar 

  • Martin MG, Pfrieger F, Dotti CG (2014) Cholesterol in brain disease: sometimes determinant and frequently implicated. EMBO Rep 15:1036–1052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marwarha G, Rhen T, Schommer T, Ghribi O (2011) The oxysterol 27-hydroxycholesterol regulates alpha-synuclein and tyrosine hydroxylase expression levels in human neuroblastoma cells through modulation of liver X receptors and estrogen receptors–relevance to Parkinson’s disease. J Neurochem 119:1119–1136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mattiazzi Usaj M, Brloznik M, Kaferle P, Zitnik M, Wolinski H, Leitner F, Kohlwein SD, Zupan B, Petrovic U (2015) Genome-wide localization study of yeast Pex11 identifies peroxisome-mitochondria interactions through the ERMES complex. J Mol Biol 427:2072–2087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McGuinness MC, Griffin DE, Raymond GV, Washington CA, Moser HW, Smith KD (1995) Tumor necrosis factor-alpha and X-linked adrenoleukodystrophy. J Neuroimmunol 61:161–169

    Article  CAS  PubMed  Google Scholar 

  • Mitchell J, Paul P, Chen HJ, Morris A, Payling M, Falchi M, Habgood J, Panoutsou S, Winkler S, Tisato V, Hajitou A, Smith B, Vance C, Shaw C, Mazarakis ND, de Belleroche J (2010) Familial amyotrophic lateral sclerosis is associated with a mutation in D-amino acid oxidase. Proc Natl Acad Sci USA 107:7556–7561

    Article  PubMed  PubMed Central  Google Scholar 

  • Miville-Godbout E, Bourque M, Morissette M, Al-Sweidi S, Smith T, Mochizuki A, Senanayake V, Jayasinghe D, Wang L, Goodenowe D, Di Paolo T (2016) Plasmalogen augmentation reverses striatal dopamine loss in MPTP mice. PLoS ONE 11:e0151020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miville-Godbout E, Bourque M, Morissette M, Al-Sweidi S, Smith T, Jayasinghe D, Ritchie S, Di Paolo T (2017) Plasmalogen precursor mitigates striatal dopamine loss in MPTP mice. Brain Res 1674:70–76

    Article  CAS  PubMed  Google Scholar 

  • Miyazaki C, Saitoh M, Itoh M, Yamashita S, Miyagishi M, Takashima S, Moser AB, Iwamori M, Mizuguchi M (2013) Altered phospholipid molecular species and glycolipid composition in brain, liver and fibroblasts of Zellweger syndrome. Neurosci Lett 552:71–75

    Article  CAS  PubMed  Google Scholar 

  • Morita M, Kurochkin IV, Motojima K, Goto S, Takano T, Okamura S, Sato R, Yokota S, Imanaka T (2000) Insulin-degrading enzyme exists inside of rat liver peroxisomes and degrades oxidized proteins. Cell Struct Funct 25:309–315

    Article  CAS  PubMed  Google Scholar 

  • Murphy S, Martin S, Parton RG (2009) Lipid droplet-organelle interactions; sharing the fats. Biochem Biophys Acta 1791:441–447

    CAS  PubMed  Google Scholar 

  • Oku M, Sakai Y (2010) Peroxisomes as dynamic organelles: autophagic degradation. FEBS J 277:3289–3294

    Article  CAS  PubMed  Google Scholar 

  • Pan Y, Khalil H, Nicolazzo JA (2015) The impact of docosahexaenoic acid on Alzheimer’s disease: is there a role of the blood-brain barrier? Curr Clin Pharmacol 10:222–241

    Article  CAS  PubMed  Google Scholar 

  • Paul P, de Belleroche J (2012) The role of D-amino acids in amyotrophic lateral sclerosis pathogenesis: a review. Amino Acids 43:1823–1831

    Article  CAS  PubMed  Google Scholar 

  • Pomatto LC, Raynes R, Davies KJ (2017) The peroxisomal Lon protease LonP2 in aging and disease: functions and comparisons with mitochondrial Lon protease LonP1. Biol Rev Camb Philos Soc 92:739–753

    Article  PubMed  Google Scholar 

  • Popp J, Meichsner S, Kolsch H, Lewczuk P, Maier W, Kornhuber J, Jessen F, Lutjohann D (2013) Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer’s disease. Biochem Pharmacol 86:37–42

    Article  CAS  PubMed  Google Scholar 

  • Prasanthi JR, Huls A, Thomasson S, Thompson A, Schommer E, Ghribi O (2009) Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on beta-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells. Mol Neurodegener 4:1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prinz WA (2014) Bridging the gap: membrane contact sites in signaling, metabolism, and organelle dynamics. J Cell Biol 205:759–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Puspita L, Chung SY, Shim JW (2017) Oxidative stress and cellular pathologies in Parkinson’s disease. Mol Brain 10:53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quinn LP, Crook B, Hows ME, Vidgeon-Hart M, Chapman H, Upton N, Medhurst AD, Virley DJ (2008) The PPARgamma agonist pioglitazone is effective in the MPTP mouse model of Parkinson’s disease through inhibition of monoamine oxidase B. Br J Pharmacol 154:226–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramsay RR, Zammit VA (2004) Carnitine acyltransferases and their influence on CoA pools in health and disease. Mol Aspects Med 25:475–493

    Article  CAS  PubMed  Google Scholar 

  • Robson LG, Dyall S, Sidloff D, Michael-Titus AT (2010) Omega-3 polyunsaturated fatty acids increase the neurite outgrowth of rat sensory neurones throughout development and in aged animals. Neurobiol Aging 31:678–687

    Article  CAS  PubMed  Google Scholar 

  • Sacchi S, Cappelletti P, Murtas G (2018) Biochemical properties of human D-amino acid oxidase variants and their potential significance in pathologies. Front Mol Biosci 5:55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sandalio LM, Romero-Puertas MC (2015) Peroxisomes sense and respond to environmental cues by regulating ROS and RNS signalling networks. Ann Bot 116:475–485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schrader M, Godinho LF, Costello JL, Islinger M (2015) The different facets of organelle interplay-an overview of organelle interactions. Front Cell Dev Biol 3:56

    Article  PubMed  PubMed Central  Google Scholar 

  • Shadfar S, Hwang CJ, Lim MS, Choi DY, Hong JT (2015) Involvement of inflammation in Alzheimer’s disease pathogenesis and therapeutic potential of anti-inflammatory agents. Arch Pharmacal Res 38:2106–2119

    Article  CAS  Google Scholar 

  • Shai N, Yifrach E, van Roermund CWT, Cohen N, Bibi C, IJ L, Cavellini L, Meurisse J, Schuster R, Zada L, Mari MC, Reggiori FM, Hughes AL, Escobar-Henriques M, Cohen MM, Waterham HR, Wanders RJA, Schuldiner M, Zalckvar E (2018) Systematic mapping of contact sites reveals tethers and a function for the peroxisome-mitochondria contact. Nat Commun 9:1761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheykhansari S, Kozielski K, Bill J, Sitti M, Gemmati D, Zamboni P, Singh AV (2018) Redox metals homeostasis in multiple sclerosis and amyotrophic lateral sclerosis: a review. Cell Death Dis 9:348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soderberg M, Edlund C, Kristensson K, Dallner G (1991) Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids 26:421–425

    Article  CAS  PubMed  Google Scholar 

  • Sugiura A, Mattie S, Prudent J, McBride HM (2017) Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes. Nature 542:251–254

    Article  CAS  PubMed  Google Scholar 

  • Tan LC, Methawasin K, Tan EK, Tan JH, Au WL, Yuan JM, Koh WP (2016) Dietary cholesterol, fats and risk of Parkinson’s disease in the Singapore Chinese Health Study. J Neurol Neurosurg Psychiatry 87:86–92

    PubMed  Google Scholar 

  • Thenganatt MA, Jankovic J (2014) Parkinson disease subtypes. JAMA Neurol 71:499–504

    Article  PubMed  Google Scholar 

  • Trompier D, Vejux A, Zarrouk A, Gondcaille C, Geillon F, Nury T, Savary S, Lizard G (2014) Brain peroxisomes. Biochimie 98:102–110

    Article  CAS  PubMed  Google Scholar 

  • Tully AM, Roche HM, Doyle R, Fallon C, Bruce I, Lawlor B, Coakley D, Gibney MJ (2003) Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer’s disease: a case-control study. Br J Nutr 89:483–489

    Article  CAS  PubMed  Google Scholar 

  • Walbrecq G, Wang B, Becker S, Hannotiau A, Fransen M, Knoops B (2015) Antioxidant cytoprotection by peroxisomal peroxiredoxin-5. Free Radic Biol Med 84:215–226

    Article  CAS  PubMed  Google Scholar 

  • Wanders RJ (2014) Metabolic functions of peroxisomes in health and disease. Biochimie 98:36–44

    Article  CAS  PubMed  Google Scholar 

  • Wanders RJ, Waterham HR, Ferdinandusse S (2015) Metabolic interplay between peroxisomes and other subcellular organelles including mitochondria and the endoplasmic reticulum. Front Cell Dev Biol 3:83

    PubMed  Google Scholar 

  • Wang W, Shinto L, Connor WE, Quinn JF (2008) Nutritional biomarkers in Alzheimer’s disease: the association between carotenoids, n-3 fatty acids, and dementia severity. J Alzheimer’s Dis 13:31–38

    Article  CAS  Google Scholar 

  • Wang X, Wang Z, Liu JZ, Hu JX, Chen HL, Li WL, Hai CX (2011) Double antioxidant activities of rosiglitazone against high glucose-induced oxidative stress in hepatocyte. Toxicol In Vitro 25:839–847

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Horn PJ, Liou LC, Muggeridge MI, Zhang Z, Chapman KD, Witt SN (2013) A peroxisome biogenesis deficiency prevents the binding of alpha-synuclein to lipid droplets in lipid-loaded yeast. Biochem Biophys Res Commun 438:452–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams C, Opalinski L, Landgraf C, Costello J, Schrader M, Krikken AM, Knoops K, Kram AM, Volkmer R, van der Klei IJ (2015) The membrane remodeling protein Pex11p activates the GTPase Dnm1p during peroxisomal fission. Proc Natl Acad Sci USA 112:6377–6382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE (2007) Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med 5:20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao Z, Wang J, Chen W, Wang P, Zeng H, Chen W (2012) Association studies of several cholesterol-related genes (ABCA1, CETP and LIPC) with serum lipids and risk of Alzheimer’s disease. Lipids Health Dis 11:163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu Z, Asahchop EL, Branton WG, Gelman BB, Power C, Hobman TC (2017) MicroRNAs upregulated during HIV infection target peroxisome biogenesis factors: implications for virus biology, disease mechanisms and neuropathology. PLoS Pathog 13:e1006360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xue-Shan Z, Juan P, Qi W, Zhong R, Li-Hong P, Zhi-Han T, Zhi-Sheng J, Gui-Xue W, Lu-Shan L (2016) Imbalanced cholesterol metabolism in Alzheimer’s disease. Clin Chim Acta 456:107–114

    Article  CAS  PubMed  Google Scholar 

  • Ye S, Huang Y, Mullendorff K, Dong L, Giedt G, Meng EC, Cohen FE, Kuntz ID, Weisgraber KH, Mahley RW (2005) Apolipoprotein (apo) E4 enhances amyloid beta peptide production in cultured neuronal cells: apoE structure as a potential therapeutic target. Proc Natl Acad Sci USA 102:18700–18705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang SO, Trimble R, Guo F, Mak HY (2010) Lipid droplets as ubiquitous fat storage organelles in C. elegans. BMC Cell Biol 11:96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Tripathi DN, Jing J, Alexander A, Kim J, Powell RT, Dere R, Tait-Mulder J, Lee JH, Paull TT, Pandita RK, Charaka VK, Pandita TK, Kastan MB, Walker CL (2015) ATM functions at the peroxisome to induce pexophagy in response to ROS. Nat Cell Biol 17:1259–1269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Yan T, Sun D, Xie C, Zheng Y, Zhang L, Yagai T, Krausz KW, Bisson WH, Yang X, Gonzalez FJ (2018) Structure-activity relationships of the main bioactive constituents of euodia rutaecarpa on aryl hydrocarbon receptor activation and associated bile acid homeostasis. Drug Metabol Dispos 46:1030–1040

    Article  CAS  Google Scholar 

  • Zhao Y, Calon F, Julien C, Winkler JW, Petasis NA, Lukiw WJ, Bazan NG (2011) Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPARgamma-mediated mechanisms in Alzheimer’s disease models. PLoS ONE 6:e15816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou P, Chen Z, Zhao N, Liu D, Guo ZY, Tan L, Hu J, Wang Q, Wang JZ, Zhu LQ (2011) Acetyl-L-carnitine attenuates homocysteine-induced Alzheimer-like histopathological and behavioral abnormalities. Rejuvenation Res 14:669–679

    Article  CAS  PubMed  Google Scholar 

  • Zhu L, Zhong M, Elder GA, Sano M, Holtzman DM, Gandy S, Cardozo C, Haroutunian V, Robakis NK, Cai D (2015) Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer’s disease pathogenesis. Proc Natl Acad Sci USA 112:11965–11970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zoeller RA, Lake AC, Nagan N, Gaposchkin DP, Legner MA, Lieberthal W (1999) Plasmalogens as endogenous antioxidants: somatic cell mutants reveal the importance of the vinyl ether. Biochem J 338:769–776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was supported by a Grant of the Korea–UK Collaborative Alzheimer’s Disease Research Project by Ministry of Health & Welfare, Republic of Korea (HI14C1913), and supported by National Research Foundation of Korea funded by the Ministry of Science & ICT (2017R1A2B4005501).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dong-Hyung Cho.

Ethics declarations

Conflict of interest

The authors declare 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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jo, D.S., Cho, DH. Peroxisomal dysfunction in neurodegenerative diseases. Arch. Pharm. Res. 42, 393–406 (2019). https://doi.org/10.1007/s12272-019-01131-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-019-01131-2

Keywords

Navigation