[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content

Advertisement

Springer Nature Link
Log in

Antioxidant Modulation of mTOR and Sirtuin Pathways in Age-Related Neurodegenerative Diseases

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

In the human body, cell division and metabolism are expected to transpire uneventfully for approximately 25 years. Then, secondary metabolism and cell damage products accumulate, and ageing phenotypes are acquired, causing the progression of disease. Among these age-related diseases, neurodegenerative diseases have attracted considerable attention because of their irreversibility, the absence of effective treatment and their relationship with social and economic pressures. Mechanistic (formerly mammalian) target of rapamycin (mTOR), sirtuin (SIRT) and insulin/insulin growth factor 1 (IGF1) signalling pathways are among the most important pathways in ageing-associated conditions, such as neurodegeneration. These longevity-related pathways are associated with a diversity of various processes, including metabolism, cognition, stress reaction and brain plasticity. In this review, we discuss the roles of sirtuin and mTOR in ageing and neurodegeneration, with an emphasis on their regulation of autophagy, apoptosis and mitochondrial energy metabolism. The intervention of neurodegeneration using potential antioxidants, including vitamins, phytochemicals, resveratrol, herbals, curcumin, coenzyme Q10 and minerals, specifically aimed at retaining mitochondrial function in the treatment of Alzheimer’s disease, Parkinson’s disease and Huntington’s disease is highlighted.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Hipkiss AR (2006) Accumulation of altered proteins and ageing: causes and effects. Exp Gerontol 41(5):464–473

    Article  CAS  PubMed  Google Scholar 

  2. Lázaro DF, Bellucci A, Brundin P, Outeiro TF (2020) Editorial: protein misfolding and spreading pathology in neurodegenerative diseases. Front Mol Neurosci 12 (312). doi:https://doi.org/10.3389/fnmol.2019.00312

  3. Agbas A (2018) Trends of protein aggregation in neurodegenerative diseases. In: Neurochemical basis of brain function and dysfunction. IntechOpen

  4. Saxton RA, Sabatini DM (2017) mTOR signaling in growth, metabolism, and disease. Cell 168(6):960–976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Salminen LE, Schofield PR, Pierce KD, Bruce SE, Griffin MG, Tate DF, Cabeen RP, Laidlaw DH et al (2017) Vulnerability of white matter tracts and cognition to the SOD2 polymorphism: a preliminary study of antioxidant defense genes in brain aging. Behav Brain Res 329:111–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Stadtman ER (2006) Protein oxidation and aging. Free Radic Res 40(12):1250–1258

    Article  CAS  PubMed  Google Scholar 

  7. G-f C, Xu T-h, Yan Y, Y-r Z, Jiang Y, Melcher K, Xu HE (2017) Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol Sin 38(9):1205–1235

    Article  CAS  Google Scholar 

  8. 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(1):32–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lee J, Kim Y, Liu T, Hwang YJ, Hyeon SJ, Im H, Lee K, Alvarez VE et al (2018) SIRT3 deregulation is linked to mitochondrial dysfunction in Alzheimer’s disease. Aging Cell 17(1):e12679

    Article  CAS  Google Scholar 

  10. Meade RM, Fairlie DP, Mason JM (2019) Alpha-synuclein structure and Parkinson’s disease - lessons and emerging principles. Mol Neurodegener 14(1):29

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Liu Y, Zhang Y, Zhu K, Chi S, Wang C, Xie A (2020) Emerging role of sirtuin 2 in Parkinson’s disease. Front Aging Neurosci 11:372

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Cattaneo E, Zuccato C, Tartari M (2005) Normal huntingtin function: an alternative approach to Huntington’s disease. Nat Rev Neurosci 6(12):919–930

    Article  CAS  PubMed  Google Scholar 

  13. Yang D, Wang C-E, Zhao B, Li W, Ouyang Z, Liu Z, Yang H, Fan P et al (2010) Expression of Huntington’s disease protein results in apoptotic neurons in the brains of cloned transgenic pigs. Hum Mol Genet 19(20):3983–3994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R (2020) Features, evaluation and treatment coronavirus (COVID-19). In: Statpearls [Internet]. StatPearls

  15. Morigaki R, Goto S (2017) Striatal vulnerability in Huntington’s disease: neuroprotection versus neurotoxicity. Brain Sci 7(6):63

    Article  PubMed Central  CAS  Google Scholar 

  16. Burtenshaw D, Hakimjavadi R, Redmond EM, Cahill PA (2017) Nox, reactive oxygen species and regulation of vascular cell fate. Antioxidants 6(4):90

    Article  PubMed Central  CAS  Google Scholar 

  17. Cenini G, Lloret A, Cascella R (2019) Oxidative stress in neurodegenerative diseases: from a mitochondrial point of view. Oxidative Med Cell Longev 2019:1–18

    Article  CAS  Google Scholar 

  18. Stefanatos R, Sanz A (2018) The role of mitochondrial ROS in the aging brain. FEBS Lett 592(5):743–758

    Article  CAS  PubMed  Google Scholar 

  19. Vessoni A, Filippi-Chiela E, Menck CF, Lenz G (2013) Autophagy and genomic integrity. Cell Death Differ 20(11):1444–1454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhao J, Goldberg AL (2016) Coordinate regulation of autophagy and the ubiquitin proteasome system by MTOR. Autophagy 12(10):1967–1970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wątroba M, Szukiewicz D (2016) The role of sirtuins in aging and age-related diseases. Adv Med Sci 61(1):52–62

    Article  PubMed  Google Scholar 

  22. Abdellatif M (2012) Sirtuins and pyridine nucleotides. Circ Res 111(5):642–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rajendran R, Garva R, Krstic-Demonacos M, Demonacos C (2011) Sirtuins: molecular traffic lights in the crossroad of oxidative stress, chromatin remodeling, and transcription. Biomed Res Int 2011

  24. Ahn B-H, Kim H-S, Song S, Lee IH, Liu J, Vassilopoulos A, Deng C-X, Finkel T (2008) A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci 105(38):14447–14452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhao L, Cao J, Hu K, He X, Yun D, Tong T, Han L (2020) Sirtuins and their biological relevance in aging and age-related diseases. Aging and Disease: 0

  26. Viana SD, Reis F, Alves R (2018) Therapeutic use of mTOR inhibitors in renal diseases: advances, drawbacks, and challenges. Oxidative Med Cell Longev 2018:1–17

    Article  CAS  Google Scholar 

  27. Liu P, Gan W, Chin YR, Ogura K, Guo J, Zhang J, Wang B, Blenis J et al (2015) PtdIns (3,4,5) P3-dependent activation of the mTORC2 kinase complex. Cancer Discov 5(11):1194–1209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Luo Y, Xu W, Li G, Cui W (2018) Weighing in on mTOR complex 2 signaling: the expanding role in cell metabolism. Oxidative Med Cell Longev 2018:1–15

    Google Scholar 

  29. Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493(7432):338–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Thibaudeau TA, Smith DM (2019) A practical review of proteasome pharmacology. Pharmacol Rev 71(2):170–197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Anderson RM, Le Couteur DG, de Cabo R (2018) Caloric restriction research: new perspectives on the biology of aging. Oxford University Press, New York

    Google Scholar 

  32. Lutz MI, Milenkovic I, Regelsberger G, Kovacs GG (2014) Distinct patterns of sirtuin expression during progression of Alzheimer’s disease. NeuroMolecular Med 16(2):405–414

    Article  CAS  PubMed  Google Scholar 

  33. Sun Y-X, Ji X, Mao X, Xie L, Jia J, Galvan V, Greenberg DA, Jin K (2014) Differential activation of mTOR complex 1 signaling in human brain with mild to severe Alzheimer’s disease. J Alzheimers Dis 38(2):437–444

    Article  CAS  PubMed  Google Scholar 

  34. Yang G, Humphrey SJ, Murashige DS, Francis D, Wang QP, Cooke KC, Neely GG, James DE (2019) RagC phosphorylation autoregulates mTOR complex 1. EMBO J 38 (3)

  35. Carrico C, Meyer JG, He W, Gibson BW, Verdin E (2018) The mitochondrial acylome emerges: proteomics, regulation by sirtuins, and metabolic and disease implications. Cell Metab 27(3):497–512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Johri A, Beal MF (2012) Mitochondrial dysfunction in neurodegenerative diseases. J Pharmacol Exp Ther 342(3):619–630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Scott I, Anderson KA, Hirschey MD (2012) Mitochondrial protein acetylation regulates metabolism. Essays Biochem 52:23–35

    Article  Google Scholar 

  38. Beretta GL, Corno C, Zaffaroni N, Perego P (2019) Role of FoxO proteins in cellular response to antitumor agents. Cancers 11(1):90

    Article  CAS  PubMed Central  Google Scholar 

  39. Wang X, Hu S, Liu L (2017) Phosphorylation and acetylation modifications of FOXO3a: independently or synergistically? Oncol Lett 13(5):2867–2872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Klotz L-O, Sánchez-Ramos C, Prieto-Arroyo I, Urbánek P, Steinbrenner H, Monsalve M (2015) Redox regulation of FoxO transcription factors. Redox Biol 6:51–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Reed SM, Quelle DE (2015) p53 acetylation: regulation and consequences. Cancers 7(1):30–69

    Article  CAS  Google Scholar 

  42. Gong P, Wang Y, Jing Y (2019) Apoptosis induction by histone deacetylase inhibitors in cancer cells: role of Ku70. Int J Mol Sci 20(7):1601

    Article  CAS  PubMed Central  Google Scholar 

  43. Hada M, Subramanian C, Andrews PC, Kwok RP (2016) Cytosolic Ku70 regulates Bax-mediated cell death. Tumor Biol 37(10):13903–13914

    Article  CAS  Google Scholar 

  44. Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, Christoffersson J, Chaabane W et al (2014) Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol 112:24–49

    Article  CAS  PubMed  Google Scholar 

  45. Verdin E, Hirschey MD, Finley LW, Haigis MC (2010) Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling. Trends Biochem Sci 35(12):669–675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Huang ML-H, Chiang S, Kalinowski DS, Bae D-H, Sahni S, Richardson DR (2019) The role of the antioxidant response in mitochondrial dysfunction in degenerative diseases: cross-talk between antioxidant defense, autophagy, and apoptosis. Oxidative Med Cell Longev 2019:1–26

    CAS  Google Scholar 

  47. Bonda DJ, Lee H-p, Kudo W, Zhu X, Smith MA, Lee H-g (2010) Pathological implications of cell cycle re-entry in Alzheimer disease. Expert Rev Mol Med 12:e19

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Yates SC, Zafar A, Hubbard P, Nagy S, Durant S, Bicknell R, Wilcock G, Christie S et al (2013) Dysfunction of the mTOR pathway is a risk factor for Alzheimer’s disease. Acta Neuropathol Commun 1(1):3

    Article  PubMed  PubMed Central  Google Scholar 

  49. Chen L, Liu L, Huang S (2008) Cadmium activates the mitogen-activated protein kinase (MAPK) pathway via induction of reactive oxygen species and inhibition of protein phosphatases 2A and 5. Free Radic Biol Med 45(7):1035–1044

    Article  CAS  PubMed  Google Scholar 

  50. Ghosh R, Pattison JS (2018) Macroautophagy and chaperone-mediated autophagy in heart failure: the known and the unknown. Oxidative Med Cell Longev 2018

  51. Pinho BR, Duarte AI, Canas PM, Moreira PI, Murphy MP, Oliveira JM (2020) The interplay between redox signalling and proteostasis in neurodegeneration: in vivo effects of a mitochondria-targeted antioxidant in Huntington’s disease mice. Free Radic Biol Med 146:372–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Condello M, Pellegrini E, Caraglia M, Meschini S (2019) Targeting autophagy to overcome human diseases. Int J Mol Sci 20(3):725

    Article  CAS  PubMed Central  Google Scholar 

  53. Thayer JA, Awad O, Hegdekar N, Sarkar C, Tesfay H, Burt C, Zeng X, Feldman RA et al (2020) The PARK10 gene USP24 is a negative regulator of autophagy and ULK1 protein stability. Autophagy 16(1):140–153

    Article  CAS  PubMed  Google Scholar 

  54. Alecu I, Bennett SA (2019) Dysregulated lipid metabolism and its role in α-synucleinopathy in Parkinson’s disease. Front Neurosci 13

  55. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443(7113):787–795

    Article  CAS  PubMed  Google Scholar 

  56. Cai Q, Tammineni P (2016) Alterations in mitochondrial quality control in Alzheimer’s disease. Front Cell Neurosci 10:24

    PubMed  PubMed Central  Google Scholar 

  57. Guo C, Sun L, Chen X, Zhang D (2013) Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res 8(21):2003–2014

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Calkins MJ, Manczak M, Mao P, Shirendeb U, Reddy PH (2011) Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer’s disease. Hum Mol Genet 20(23):4515–4529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Cai Q, Jeong YY (2020) Mitophagy in Alzheimer’s disease and other age-related neurodegenerative diseases. Cells 9(1):150

    Article  CAS  PubMed Central  Google Scholar 

  60. Reeve A, Ludtmann MH, Angelova P, Simcox E, Horrocks M, Klenerman D, Gandhi S, Turnbull D et al (2015) Aggregated α-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons. Cell Death Dis 6(7):e1820–e1820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. McColgan P, Tabrizi SJ (2018) Huntington’s disease: a clinical review. Eur J Neurol 25(1):24–34

    Article  CAS  PubMed  Google Scholar 

  62. Yablonska S, Ganesan V, Ferrando LM, Kim J, Pyzel A, Baranova OV, Khattar NK, Larkin TM et al (2019) Mutant huntingtin disrupts mitochondrial proteostasis by interacting with TIM23. Proc Natl Acad Sci 116(33):16593–16602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Guarente L (2013) Calorie restriction and sirtuins revisited. Genes Dev 27(19):2072–2085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, Zhao W, Thiyagarajan M et al (2006) Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem 281(31):21745–21754

    Article  CAS  PubMed  Google Scholar 

  65. Tang Z, Baykal AT, Gao H, Quezada HC, Zhang H, Bereczki E, Serhatli M, Baykal B et al (2014) mTor is a signaling hub in cell survival: a mass-spectrometry-based proteomics investigation. J Proteome Res 13(5):2433–2444

    Article  CAS  PubMed  Google Scholar 

  66. Adav SS, Sze SK (2020) Hypoxia-induced degenerative protein modifications associated with aging and age-associated disorders. Aging and Disease: 0

  67. Schirinzi T, Martella G, Imbriani P, Di Lazzaro G, Franco D, Colona VL, Alwardat M, Salimei PS, Mercuri NB, Pierantozzi M (2019) Dietary vitamin E as a protective factor for Parkinson’s disease: clinical and experimental evidence. Front Neurol 10

  68. Eckert GP (2019) The role of vitamin E in aging and Alzheimer’s disease. In: Vitamin E in human health. Springer, pp. 325–344

  69. Yang F, Wolk A, Håkansson N, Pedersen NL, Wirdefeldt K (2017) Dietary antioxidants and risk of Parkinson’s disease in two population-based cohorts. Mov Disord 32(11):1631–1636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Miyake Y, Fukushima W, Tanaka K, Sasaki S, Kiyohara C, Tsuboi Y, Yamada T, Oeda T et al (2011) Dietary intake of antioxidant vitamins and risk of Parkinson’s disease: a case–control study in Japan. Eur J Neurol 18(1):106–113

    Article  CAS  PubMed  Google Scholar 

  71. Hughes KC, Gao X, Kim IY, Rimm EB, Wang M, Weisskopf MG, Schwarzschild MA, Ascherio A (2016) Intake of antioxidant vitamins and risk of Parkinson’s disease. Mov Disord 31(12):1909–1914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kryscio RJ, Abner EL, Caban-Holt A, Lovell M, Goodman P, Darke AK, Yee M, Crowley J et al (2017) Association of antioxidant supplement use and dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium Trial (PREADViSE). JAMA Neurol 74(5):567–573

    Article  PubMed  PubMed Central  Google Scholar 

  73. Evatt ML, DeLong MR, Kumari M, Auinger P, McDermott MP, Tangpricha V (2011) High prevalence of hypovitaminosis D status in patients with early Parkinson disease. Arch Neurol 68(3):314–319

    Article  PubMed  Google Scholar 

  74. Naia L, Rosenstock TR, Oliveira AM, Oliveira-Sousa SI, Caldeira GL, Carmo C, Laço MN, Hayden MR et al (2017) Comparative mitochondrial-based protective effects of resveratrol and nicotinamide in Huntington’s disease models. Mol Neurobiol 54(7):5385–5399

    Article  CAS  PubMed  Google Scholar 

  75. Sawda C, Moussa C, Turner RS (2017) Resveratrol for Alzheimer’s disease. Ann N Y Acad Sci 1403(1):142–149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Dysken MW, Sano M, Asthana S, Vertrees JE, Pallaki M, Llorente M, Love S, Schellenberg GD et al (2014) Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA 311(1):33–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Belitskaya‐Lévy I, Dysken M, Guarino P, Sano M, Asthana S, Vertrees JE, Pallaki M, Llorente M, Love S, Schellenberg G (2018) Impact of apolipoprotein E genotypes on vitamin E and memantine treatment outcomes in Alzheimer’s disease. Alzheimer's & Dementia: Translational Research & Clinical Interventions 4:344–349

  78. Sun AY, Wang Q, Simonyi A, Sun GY (2010) Resveratrol as a therapeutic agent for neurodegenerative diseases. Mol Neurobiol 41(2–3):375–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Ma T, Tan M-S, Yu J-T, Tan L (2014) Resveratrol as a therapeutic agent for Alzheimer’s disease. Biomed Res Int 2014:1–13

    Google Scholar 

  80. Lu K-T, Ko M-C, Chen B-Y, Huang J-C, Hsieh C-W, Lee M-C, Chiou RY, Wung B-S et al (2008) Neuroprotective effects of resveratrol on MPTP-induced neuron loss mediated by free radical scavenging. J Agric Food Chem 56(16):6910–6913

    Article  CAS  PubMed  Google Scholar 

  81. Jin F, Wu Q, Lu Y-F, Gong Q-H, Shi J-S (2008) Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson’s disease in rats. Eur J Pharmacol 600(1–3):78–82

    Article  CAS  PubMed  Google Scholar 

  82. Pourhanifeh MH, Shafabakhsh R, Reiter RJ, Asemi Z (2019) The effect of resveratrol on neurodegenerative disorders: Possible protective actions against autophagy, apoptosis, inflammation and oxidative stress. Curr Pharm Des 25(19):2178–2191

    Article  CAS  PubMed  Google Scholar 

  83. Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41(1):40–59

    Article  CAS  PubMed  Google Scholar 

  84. Darvesh AS, Carroll RT, Bishayee A, Novotny NA, Geldenhuys WJ, Van der Schyf CJ (2012) Curcumin and neurodegenerative diseases: a perspective. Expert Opin Investig Drugs 21(8):1123–1140

    Article  CAS  PubMed  Google Scholar 

  85. Noguchi-Shinohara M, Hamaguchi T, Yamada M (2019) The potential role of curcumin in treatment and prevention for neurological disorders. In: Curcumin for neurological and psychiatric disorders. Elsevier, pp. 85–103

  86. Elifani F, Amico E, Pepe G, Capocci L, Castaldo S, Rosa P, Montano E, Pollice A, Madonna M, Filosa S (2019) Curcumin dietary supplementation ameliorates disease phenotype in an animal model of Huntington’s disease. Hum Mol Genet

  87. Dumont M, Kipiani K, Yu F, Wille E, Katz M, Calingasan NY, Gouras GK, Lin MT et al (2011) Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis 27(1):211–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. McGarry A, McDermott M, Kieburtz K, de Blieck EA, Beal F, Marder K, Ross C, Shoulson I et al (2017) A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. Neurology 88(2):152–159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Apostolova N, Victor VM (2015) Molecular strategies for targeting antioxidants to mitochondria: therapeutic implications. Antioxid Redox Signal 22(8):686–729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This review is part of a research study financially supported by the Ministry of Higher Education Grant (FRGS/1/2019/SKK08/UKM/01/4).

Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Level 17, Preclinical Building, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000, Kuala Lumpur, Malaysia

    Asmaa Abdullah, Nuraqila Mohd Murshid & Suzana Makpol

Authors
  1. Asmaa Abdullah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nuraqila Mohd Murshid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suzana Makpol
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SM developed the concept and revised the manuscript. AA and NMM analysed the literature and wrote and edited the draft of the manuscript. NMM drew the diagrams and prepared the table.

Corresponding author

Correspondence to Suzana Makpol.

Ethics declarations

Competing Interests

The authors declare that they have no competing interests.

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

Abdullah, A., Mohd Murshid, N. & Makpol, S. Antioxidant Modulation of mTOR and Sirtuin Pathways in Age-Related Neurodegenerative Diseases. Mol Neurobiol 57, 5193–5207 (2020). https://doi.org/10.1007/s12035-020-02083-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-020-02083-1

Keywords

Search

Navigation