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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

(English title: Physiological Journal)

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2019; 65(3): 61-72


Nonel approaches to correction of mitochondrial dysfunction and oxidative disorders in Parkinson’s disease

O. Gonchar1, I. Mankovska1, K. Rozova1, L. Bratus1, I. Karaban2

  1. O.O.Bogomoletz Institute of Physiology National Academy of Sciences of Ukraine, Kyiv, Ukraine
  2. D.F. Chebotarev Institute of Gerontology National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz65.03.061


Abstract

Mitochondrial dysfunction has been widely implicated in the neuronal degeneration in Parkinson’s disease (PD). The uses of mitochondria-targeted protective compounds that prevent or minimize a wide range of mitochondrial defects constitute potential therapeutic strategies in the prevention and treatment of neuronal degeneration in PD. This review discusses the latest findings in this field obtained in PD patients and animal and cellular models of PD with focusing on the effects of pharmacological agents on mitochondrial biogenesis, fission, fusion, mitophagy machinery, and transcription of endogenous cytoprotective antioxidant enzymes. We have also presented the data concerning the technologies for research and screening novel bioactive molecules to target mitochondrial dysfunction in Parkinson’s disease.

Keywords: Parkinson’s disease, mitochondrial dysfunction, mitochondria-targeted protective compounds.

References

  1. Frank C, Pari G, Rossiter JP. Approach to diagnosis of Parkinson disease. Can Fam Physician. 2006;52: 862-8.
  2.  
  3. Hudson G. The ageing brain, mitochondria and neurodegeneration. In: Reeve AK, Simcox EM, Duchen MR, Turnbull DM, eds. Mitochondrial Dysfunction in Neurodegenerative Disorders. 2nd ed. Springer Int Publishing 2016;59-80. CrossRef.1007/978-3-319-28637-2_3
  4.  
  5. Beal MF. Mitochondria take center stage in aging and neurodegeneration. Ann Neurol. 2005;58:495-505. CrossRef PubMed
  6.  
  7. Chaturvedi RK and Beal M. Mitochondrial approaches for neuroprotection. Ann NY Acad Sci. 2008;1147:395-412. CrossRef PubMed PubMedCentral
  8.  
  9. Langston JW, Ballard P, Tetrud JW and Irwin I. Chronic Parkinsonism in humans due to a product of meperidineanalog synthesis. Science. 1983;219:979-80. - CrossRef PubMed
  10.  
  11. Jenner P. Oxidative stress in Parkinson's disease. Ann Neurol. 2003; 53 (suppl 3):S26-36 doi:10.1002/ana.10483 CrossRef PubMed
  12.  
  13. Lin MT and Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443:787-95. CrossRef PubMed
  14.  
  15. Pan-Montojo F, Schwarz M, Winkler C, Arnhold M, O'Sullivan GA, Pal A, Said J, Marsico G, Verbavatz JM, Rodrigo-Angulo M, Gille G, Funk RH, Reichmann H. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep. 2012;2:898. CrossRef PubMed PubMedCentral
  16.  
  17. Majd S, Power JH, Grantham HJ. Neuronal response in Alzheimer's and Parkinson's disease: the effect of toxic proteins on intracellular pathways. BMC Neurosci. 2015;16:69. CrossRef PubMed PubMedCentral
  18.  
  19. Cannon JR, Greenamyre JT. Neurotoxic in vivo models of Parkinson's disease recent advances. Prog Brain Res. 2010;184:17-33. CrossRef.1016/S0079-6123(10)84002-6
  20.  
  21. Picard M, McManus MJ. Mitochondrial signaling and neurodegeneration. In: Reeve AK, Simcox EM, Duchen MR, Turnbull DM, eds. Mitochondrial Dysfunction in Neurodegenerative Disorders. 2nd ed. Springer Int Publishing 2016;107-37. CrossRef.1007/978-3-319-28637-2_5
  22.  
  23. Smith RAJ, Hartley RC, Cocheme HM, Murphy MP. Mitochondrial pharmacology. Trends Pharm Sci. 2012;33(6):341-52. CrossRef PubMed
  24.  
  25. Hudson G, Nalls M, Evans JR, Breen DP, Winder-Rhodes S, Morrison KE, Morris HR, Williams-Gray CH, Barker RA, Singleton AB, Hardy J, Wood NE, Burn DJ, Chinnery PF. Two-stage association study and meta-analysis of mitochondrial DNA variants in Parkinson's disease. Neurology. 2013;80:2042-48. CrossRef PubMed PubMedCentral
  26.  
  27. Leonard JV, Schapira AH. Mitochondrial respiratory chain disorders II: neurodegenerative disorders and nuclear gene defects. Lancet 2000;355:389-94. CrossRef.1016/S0140-6736(99)05226-5
  28.  
  29. Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi K, Ariga H. DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep. 2004;5:213-18. CrossRef PubMed PubMedCentral
  30.  
  31. Moore DJ, Zhang L, Troncoso J, Lee MK, Hattori N, Mizuno Y, Dawson TM, Dawson VL. Association of DJ-1 and parkin mediated by pathogenic DJ-1 mutations and oxidative stress. Hum Mol Genet. 2005;14:71-84. CrossRef PubMed
  32.  
  33. Schapira AH. Mitochondria in the aetiology and pathogenesis of Parkinson's disease. Lancet Neurol. 2008;7:97-109. CrossRef.1016/S1474-4422(07)70327-7
  34.  
  35. Bose A and Beal MF. Mitochondrial dysfunction in Parkinson's disease. J Neurochem. 2016; 139(Suppl.1):216-31. CrossRef PubMed
  36.  
  37. Ryan BJ, Hoek S, Fon EA, Wade-Martins R. Mitochondrial dysfunction and mitophagy in Parkinson's: From familial to sporadic disease. Trends Biochem Sci. 2015; 40:200-10. CrossRef PubMed
  38.  
  39. Truban D, Hou X, Caulfield TR, Fiesel FC, Springer W. PINK 1, Parkin, and Mitochondrial Quality Control: What can we learn about Parkinson's disease pathobiology? J Parkinson's disease. 2017;7:13-29. CrossRef PubMed PubMedCentral
  40.  
  41. Schapira HV, Olanow CW, Greenamyre JT, Bezard E. Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapeutic perspectives. The Lancet. 2014;384:545-55. CrossRef.1016/S0140-6736(14)61010-2
  42.  
  43. Stewart VC, Heales SJ. Nitric oxide-induced mitochondrial dysfunction: Implications for neurodegeneration. Free Radic Biol Med. 2003; 34:287-303. CrossRef.1016/S0891-5849(02)01327-8
  44.  
  45. Henchcliffe C and Beal MF. Mitochondrial biology and oxidative stress in Parkinson's disease pathogenesis. Nature Clin Pract Neurol. 2008;4:600-09. CrossRef PubMed
  46.  
  47. Narendra DP, Youle RJ. Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial quality control. Antioxid Redox Signal. 2011;14:1929-38. CrossRef PubMed PubMedCentral
  48.  
  49. Perier C, Bové J, Dehay B, Jackson-Lewis V, Rabinovitch PS, Przedborski S, and Vila M. Apoptosis-inducing factor deficiency sensitizes dopaminergic neurons to parkinsonian neurotoxins. Ann Neurol. 2010;68:184-92. CrossRef PubMed
  50.  
  51. Franco-Iborra S, Vila M, Perier C. The Parkinson's disease mitochondrial hypothesis: where are we at? Neuroscientist 2016;22:266-77. CrossRef PubMed
  52.  
  53. Milane L, Trivedi M, Singh A, Talekar M, Amiji M. Mitochondrial biology, targets, and drug delivery. J Control Release. 2015;207:40-58. CrossRef PubMed
  54.  
  55. Teicher BA, Holden SA, Cathcart KN. Efficacy of Pt(Rh-123)2 as a radiosensitizer with fractionated X rays. Int J Radiat Oncol Biol Phys. 1987;13:1217-24. CrossRef.1016/0360-3016(87)90197-0
  56.  
  57. Szeto HH, Schiller PW. Novel therapies targeting inner mitochondrial membrane - from discovery to clinical development. Pharm Res. 2011; 28:2669-79. CrossRef PubMed
  58.  
  59. Yousif LF, Stewart KM, Kelley SO. Targeting mitochondria with organelle-specific compounds: strategies and applications. Chem Biochem. 2009;10:1939-50. CrossRef PubMed
  60.  
  61. Snow BJ, Rolfe FL, Lockhart MM, Frampton CM, O'Sullivan JD, Fung V, Smith RA, Murphy MP, Taylor KM. A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease. Mov Disord. 2010; 25:1670-74. CrossRef PubMed
  62.  
  63. Smith RA and Murphy MP. Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Ann NY Acad Sci. 2010;1201:96-103. CrossRef PubMed
  64.  
  65. Ghosh A, Solesio ME, Prime TA, Logan A, Murphy MP. Neuroprotection by a mitochondria-targeted drug in a Parkinson's disease model. Free Radic Biol Med. 2010;49:1674-84. CrossRef PubMed PubMedCentral
  66.  
  67. Twig G, Shirihai O S. The interplay between mitochondrial dynamics and mitophagy. Antioxid Redox Signal. 2011;14:1939-51. CrossRef PubMed PubMedCentral
  68.  
  69. Patki G, Lau Y-S. Melatonin protects against neurobehavioral and mitochondrial deficits in a chronic mouse model of Parkinson's disease. Pharmacol Biochem Behavior. 2011;99(4):704-11. CrossRef PubMed PubMedCentral
  70.  
  71. Dabbeni-Sala F, di Santo S, Franceschini D, Skaper SD, and Giusti P. Melatonin protects against 6-OHDAinduced neurotoxicity in rats: a role for mitochondrial complex I activity. FASEB J. 2001;15(1):164-70. CrossRef PubMed
  72.  
  73. Strathearn KE, Yousef GG, Grace MH, Roy SL, Tambe MA, Ferruzzi MG, Wu QL, Simon JE, Lila MA, Rochet JC. Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinson's disease. Brain Res. 2014; 1555:60-77. CrossRef PubMed PubMedCentral
  74.  
  75. Geed M, Garabadu D, Ahmad A, and Krishnamurthy S. Silibinin pretreatment attenuates biochemical and behavioral changes induced by intrastriatal MPP+ injection in rats. Pharmacol Biochem Behavior. 2014;117:92-103. CrossRef PubMed
  76.  
  77. Guo S, Bezard E, and Zhao B. Protective effect of green tea polyphenols on the SH-SY5Y cells against 6-OHDA induced apoptosis through ROS-NO pathway. Free Radic Biol Med. 2005;39(5):682-95. CrossRef PubMed
  78.  
  79. Hwang CK, Chun HS. Isoliquiritigenin isolated from licorice Glycyrrhiza uralensis prevents 6-hydroxydopamine induced apoptosis in dopaminergic neuron. Biosci Biotechnol Biochem. 2012;76(3):536-43. CrossRef PubMed
  80.  
  81. Kim HG, Ju MS, Kim DH, Hong J, Cho SH, Cho KH, Park W, Lee EH, Kim SY, Oh MS Protective effects of Chunghyuldan against ROS-mediated neuronal cell death in models of Parkinson's disease. Basic Clin Pharmacol Toxicol. 2010; 107 (6):958-64. CrossRef PubMed
  82.  
  83. Tamilselvam K, Braidy N, Manivasagam T, Essa MM, Prasad NR, Karthikeyan S, Thenmozhi AJ, Selvaraju S, Guillemin GJ. Neuroprotective effects of hesperidin, a plant flavanone, on rotenone induced oxidative stress and apoptosis in a cellular model for Parkinson's disease. Oxid Med Cell Longev. 2013;2013:102741. CrossRef PubMed PubMedCentral
  84.  
  85. Karuppagounder SS, Madathil SK, Pandey M, Haobam R, Rajamma U, Mohanakumar KP. Quercetin up-regulates mitochondrial complex I activity to protect against programmed cell death in rotenone model of Parkinson's disease in rats. Neuroscience. 2013;236:136-48. CrossRef PubMed
  86.  
  87. Bournival J, Plouffe M, Renaud J, Provencher C, Martinoli M-G. Quercetin and sesamin protect dopaminergic cells from MPP+-induced neuroinflammation in a microglial (N9)-neuronal (PC12) coculture system. Oxid Med Cell Longev. 2012; 11. CrossRef PubMed PubMedCentral
  88.  
  89. Wang Y-H, Yu H-T, Pu X-P, Du G-H. Baicalein prevents 6-hydroxydopamine-induced mitochondrial dysfunction in SH-SY5Y cells via inhibition of mitochondrial oxidation and up-regulation of DJ-1 protein expression. Molecules. 2013 ;18(12):14726-38. CrossRef PubMed PubMedCentral
  90.  
  91. Li XX, He GR, Mu X, Xu B, Tian S, Yu X, Meng FR, Xuan ZH, Du GH. Protective effects of baicalein against rotenone-induced neurotoxicity in PC12 cells and isolated rat brain mitochondria. Eur J Pharmacol. 2012;674(2- 3):227-33. CrossRef PubMed
  92.  
  93. Jagatha B, Mythri RB, Vali S, Bharath M. M. S. Curcumin treatment alleviates the effects of glutathione depletion in vitro and in vivo: therapeutic implications for Parkinson's disease explained via in silico studies. Free Radic Biol Med. 2008;44(5):907-17. CrossRef PubMed
  94.  
  95. Liu Z, Yu Y, Li X, Ross CA, Smith WW. Curcumin protects against A53T alpha-synuclein-induced toxicity in a PC12 inducible cell model for Parkinsonism. Pharmacol Res. 2011;63(5):439-44. CrossRef PubMed
  96.  
  97. Subramaniam SR and Ellis EM. Neuroprotective effects of umbelliferone and esculetin in a mouse model of Parkinson's disease. J Neurosci Res. 2013;91(3):453-61. CrossRef PubMed
  98.  
  99. Liu WB, Zhou J, Qu Y, Li X, Lu CT, Xie KL, Sun XL, Fei Z. Neuroprotective effect of osthole on MPP+-induced cytotoxicity in PC12 cells via inhibition of mitochondrial dysfunction and ROS production. Neurochem Int. 2010;57(3):206-15. CrossRef PubMed
  100.  
  101. Yi F, He X, Wang D. Lycopene protects against MPP+-induced cytotoxicity by maintaining mitochondrial function in SH-SY5Y cells. Neurochem Res. 2013;38(8):1747-57. CrossRef PubMed
  102.  
  103. Kaur H, Chauhan S, Sandhir R. Protective effect of lycopene on oxidative stress and cognitive decline in rotenone induced model of Parkinson's disease. Neurochemic Res. 2011 ;36(8):1435-43. CrossRef PubMed
  104.  
  105. Seidl SE and Potashkin JA. The promise of neuroprotective agents in Parkinson's disease.Front Neurol; 2011; 2: 68. CrossRef PubMed PubMedCentral
  106.  
  107. Helliwell SB.. Development of treatments and therapies to target mitochondrial dysfunction. In: Reeve AK, Simcox EM, Duchen MR, Turnbull DM, eds. Mitochondrial Dysfunction in Neurodegenerative Disorders. Springer 2nd ed. Int Publishing 2016;349-371. CrossRef.1007/978-3-319-28637-2_15
  108.  
  109. Moosmann B and Behl C. Antioxidants as treatment for neurodegenerative disorders. Expert Opin Invest Drugs. 2002;11:1407-35. CrossRef PubMed
  110.  
  111. van Muiswinkel FL and Kuiperij HB. The Nrf2-ARE signalling pathway: promising drug target to combat oxidative stress in neurodegenerative disorders. Curr Drug Targets CNS Neurol Disord. 2005;4:267-81. CrossRef PubMed
  112.  
  113. Nguyen T, Sherratt PJ, Pickett CB. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol. 2003; 43:233-60. CrossRef PubMed
  114.  
  115. Surh YJ, Kundu JK, Na HK. Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med. 2008;74:1526-39. CrossRef PubMed
  116.  
  117. Wu KC, McDonald PR, Liu J, Klaassen CD. Screening of natural compounds as activators of the Keap 1-Nrf2 pathway. Planta Med. 2013;80:97-104. CrossRef PubMed PubMedCentral
  118.  
  119. Calkins MJ, Johnson DA, Townsend JA, Vargas MR, Dowell JA, Williamson TP, Kraft AD, Lee JM, Li J, Johnson JA. The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative disease. Antioxid Redox Signal. 2009;11:497-508. CrossRef PubMed PubMedCentral
  120.  
  121. Lee C, Park GH, Lee SR, Jang JH. Attenuation of betaamyloid-induced oxidative cell death by sulforaphane via activation of NF-E2-related factor 2. Oxid Med Cell Longev. 2013; 2013 :313510. CrossRef PubMed PubMedCentral
  122.  
  123. Eggler AL, Gay KA, Mesecar AD. Molecular mechanisms of natural products in chemoprevention: induction of cytoprotective enzymes by Nrf2. Mol Nutr Food Res. 2008;52 (Suppl. 1):S84-S94. CrossRef PubMed
  124.  
  125. Yang L, Zhao K, Calingasan NY, Luo G, Szeto HH, Beal MF. Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. Antioxid Redox Signal. 2009;11:2095-2104. CrossRef PubMed PubMedCentral
  126.  
  127. Miclea A, Leussink VI, Hartung HP, Gold R, and Hoepner R. Safety and efficacy of dimethyl fumarate in multiple sclerosis: a multi-center observational study. J Neurol. 2016. CrossRef PubMed
  128.  
  129. Ahuja M, Ammal Kaidery N, Yang L, Calingasan N, Smirnova N, Gaisin A, Gaisina IN, Gazaryan I, Hushpulian DM, Kaddour-Djebbar I, Bollag WB, Morgan JC, Ratan RR, Starkov AA, Beal MF, Thomas B. Distinct Nrf2 signaling mechanisms of fumaric acid esters and their role in neuroprotection against 1-methyl-4- phenyl-1,2,3,6- tetrahydropyridine-induced experimental Parkinson's-like disease. J Neurosci. 2016;36:6332-51. CrossRef PubMed PubMedCentral
  130.  
  131. Wenz T. Regulation of mitochondrial biogenesis and PGC-1alpha under cellular stress. Mitochondrion. 2013;13(2):134-42. CrossRef PubMed
  132.  
  133. Chen H and Chan DC. Mitochondrial dynamics in mammals. Curr Top Dev Biol. 2004; 59:119-44. CrossRef.1016/S0070-2153(04)59005-1
  134.  
  135. Mishra P, Carelli V, Manfredi G, Chan DC. Proteolytic cleavage of Opa 1 stimulates mitochondrial inner membrane fusion and couples fusion to oxidative phosphorylation. Cell Metab. 2014;19(4):630-41. CrossRef PubMed PubMedCentral
  136.  
  137. Mourier A. Mitochondrial dynamics and neurodegeneration. In: Reeve AK, Simcox EM, Duchen MR, Turnbull DM, eds. Mitochondrial Dysfunction in Neurodegenerative Disorders. Springer 2nd ed. Int Publishing 2016;175-191. CrossRef.1007/978-3-319-28637-2_7
  138.  
  139. Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Publ Gr. 2011;12(1):9-14. CrossRef PubMed PubMedCentral
  140.  
  141. Wang D, Wang J, Bonamy GM, Meeusen S, Brusch RG, Turk C, Yang P, Schultz PG. A small molecule promotes mitochondrial fusion in mammalian. Angew Chem. 2012;51:9302-5. CrossRef PubMed
  142.  
  143. Yue W, Chen Z, Liu H, Yan C, Chen M, Feng D, Yan C, Wu H, Du L, Wang Y, Liu J, Huang X, Xia L, Liu L, Wang X, Jin H, Wang J, Song Z, Hao X, Chen Q. A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30. Cell Res. 2014; 24(4) :482-96. CrossRef PubMed PubMedCentral
  144.  
  145. Rappold PM, Cui M, Grima JC, Fan RZ, de Mesy-Bentley KL, Chen L, Zhuang X, Bowers WJ, Tieu K. Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo. Nat Commun. 2014; 5:5244. CrossRef PubMed PubMedCentral
  146.  
  147. Taymans JM, Greggio E. LRRK2 Kinase Inhibition as a Therapeutic Strategy for Parkinson's Disease. Where Do We Stand ? Curr Neuropharmacol. 2016;14(3):214-25. CrossRef PubMed PubMedCentral
  148.  
  149. Ventura-Clapier R, Garnier A, Veksler V.Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res. 2008;79:208-17. CrossRef PubMed
  150.  
  151. Mudò G, Mäkelä J, Di Liberto V, Tselykh TV, Olivieri M, Piepponen P, Eriksson O, Mälkiä A, Bonomo A, Kairisalo M, Aguirre JA, Korhonen L, Belluardo N, Lindholm D. Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson's disease. Cell Mol Life Sci. 2012; 69:1153-65. CrossRef PubMed
  152.  
  153. Borra MT, Smith BC, Denu JM. Mechanism of human SIRT 1 activation by resveratrol. J Biol Chem. 2005;280(17):17187-95. CrossRef PubMed
  154.  
  155. Hasegawa K, Yasuda T, Shiraishi C, Fujiwara K, Przedborski S, Mochizuki H, Yoshikawa K. Promotion of mitochondrial biogenesis by necdin protects neurons against mitochondrial insults. Nat Commun. 2016;7:10943. CrossRef PubMed PubMedCentral
  156.  
  157. Otten EG, Manni D, Korolchuk VI. Mitochondrial degradation, autophagy and neurodegenerative disease. In: Reeve AK, Simcox EM, Duchen MR, Turnbull DM, eds. Mitochondrial Dysfunction in Neurodegenerative Disorders. 2nd ed. Springer Int Publishing 2016;255-278. CrossRef.1007/978-3-319-28637-2_11
  158.  
  159. Corti O, Lesage S, Brice A. What genetics tells us about the causes and mechanisms of Parkinson's disease. Physiol Rev. 2011;91(4):1161-218. CrossRef PubMed
  160.  
  161. Trempe JF and Fon EA. Structure and function of Parkin, PINK 1, and DJ-1, the three musketeers of neuroprotection. Front Neurol. 2013;4:38. CrossRef PubMed PubMedCentral
  162.  
  163. Palacino JJ, Sagi D, Goldberg MS, Krauss S, Motz C, Wacker M, Klose J, Shen J. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem. 2004;279(18):18614-22. CrossRef PubMed
  164.  
  165. Gandhi S, Wood-Kaczmar A, Yao Z, Plun-Favreau H, Deas E, Klupsch K, Downward J, Latchman DS, Tabrizi SJ, Wood NW, Duchen MR, Abramov AY. PINK 1 - associated Parkinson's disease is caused by neuronal vulnerability to calcium-induced cell death. Mol cell. 2009;33(5):627-38. CrossRef PubMed PubMedCentral
  166.  
  167. Canet-Avilés RM, Wilson MA, Miller DW, Ahmad R, McLendon C, Bandyopadhyay S, Baptista MJ, Ringe D, Petsko GA, Cookson MR The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci USA. 2004;101(24):9103-8. CrossRef PubMed PubMedCentral
  168.  
  169. Thomas KJ, McCoy MK, Blackinton J, Beilina A, van der Brug M, Sandebring A, Miller D, Maric D, CedazoMinguez A, Cookson MR. DJ-1 acts in parallel to the PINK 1/parkin pathway to control mitochondrial function and autophagy. Hum Mol Genet. 2011;20(1):40-50.
  170. Bian M, Liu J, Hong X, Yu M, Huang Y, Sheng Z, Fei J, Huang F. Overexpression of parkin ameliorates dopaminergic neurodegeneration induced by 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine in mice. PLoS Biol. 2012;7(6):e39953. CrossRef PubMed PubMedCentral
  171.  
  172. Santos RX, Correia SC, Carvalho C, Cardoso S, Santos MS, Moreira PI. Mitophagy in neurodegeneration:an opportunity for therapy? Curr Drug Targets. 2011; 12(6):790-9. CrossRef PubMed
  173.  
  174. Cheng Y, Ren X, Hait WN, Yang JM. Therapeutic targeting of autophagy in disease: biology and pharmacology. Pharmacol Rev. 2013;65(4):1162-97. CrossRef PubMed PubMedCentral
  175.  
  176. Hasson SA, Fogel AI, Wang C, MacArthur R, Guha R, Heman-Ackah S, Martin S, Youle RJ, Inglese J. Chemogenomic profiling of endogenous PARK2 expression using a genome-edited coincidence reporter. ACS Chem Biol. 2015;10:1188-97. CrossRef PubMed
  177.  
  178. Chambers JW, Pachori A, Howard S, Ganno M, Hansen D Jr, Kamenecka T, Song X, Duckett D, Chen W, Ling YY, Cherry L, Cameron MD, Lin L, Ruiz CH, Lograsso P. Small molecule c-jun-N-terminal kinase inhibitors protect dopaminergic neurons in a model of Parkinson's disease. ACS Chem Neurosci. 2011;2(4):198-206. CrossRef PubMed PubMedCentral
  179.  
  180. Hertz NT, Berthet A, Sos ML, Thorn KS, Burlingame AL, Nakamura K, and Shokat KM. A neo-substrate that amplifies catalytic activity of Parkinson's-disease-related kinase PINK1. Cell. 2013;154:737-47. CrossRef PubMed PubMedCentral
  181.  
  182. Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q, Foreman O, Kirkpatrick DS & Sheng M. The mitochondrial deubiquitinase USP30 opposes parkinmediated mitophagy. Nature. 2014;510:370-75. CrossRef PubMed
  183.  
  184. Mankovska IM., Rosova KV, Gonchar OO, Nosar VI, Bratus LV, Drevitska TI, Karasevich NV, Karaban IM. Effect of Capicor on the Parkinson's disease pathogenic links. Fiziol Zh. 2018;64(1):16-24 [Ukraine]. CrossRef
  185.  
  186. Gardian G, Yang L, Cleren C, Calingasan NY, Klivenyi P, Beal MF. Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity. Neuromolecular Med. 2004;5:235-241. CrossRef.1385/NMM:5:3:235
  187.  
  188. Inden M, Kitamura Y, Takeuchi H, Yanagida T, Takata K, Kobayashi Y, Taniguchi T, Yoshimoto K, Kaneko M, Okuma Y, Taira T, Ariga H, and Shimohama S. Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone. J Neurochem. 2007;101:1491-1504. CrossRef PubMed
  189.  
  190. Wilkins HM, Carl SM, Swerdlow RH. Cytoplasmic hybrid (cybrid) cell lines as a practical model for mitochondriopathies. Redox Biol. 2014;2(1):619-31. CrossRef PubMed PubMedCentral
  191.  
  192. Cooper O, Seo H, Andrabi S, Guardia-laguarta C. Pharmacological rescue of mitochondrial deficis in iPSC-derived neural cells from patients with familial Parkinson's disease. Sci Transl Med. 2012;4(141):141-90. CrossRef PubMed PubMedCentral
  193.  
  194. Sanders LH, Laganière J, Cooper O, Mak SK, Vu BJ, Huang YA, Paschon DE, Vangipuram M, Sundararajan R, Urnov FD, Langston JW, Gregory PD, Zhang HS, Greenamyre JT, Isacson O, Schüle B. LRRK2 mutations cause mitochondrial DNA damage in iPSC-derived neural cells from Parkinson's disease patients: reversal by gene correction. Neurobiol Dis. 2014;62:381-6. CrossRef PubMed PubMedCentral
  195.  
  196. Tang FL, Liu W, Hu JX, Erion JR, Ye J, Mei L, Xiong WC. VPS35 deficiency or mutation causes dopaminergic neuronal loss by impairing mitochondrial fusion and function. Cell Rep. 2015;12:1631-43. CrossRef PubMed PubMedCentral
  197.  
  198. Dong J, Li S, Mo JL, Cai HB, Le WD. Nurr1-based therapies for Parkinson's disease. CNS Neurosci Ther. 2016;22:351-59. CrossRef PubMed PubMedCentral
  199.  
  200. Lotharius J, Dugan LL, O'Malley KL. Distinct mechanisms underlie neurotoxin-mediated cell death in cultured dopaminergic neurons. J Neurosci Res. 1999;19(4):1284-93. CrossRef
  201.  
  202. Jin H, Chen WQ, Tang XW, Chiang LY, Yang CY, Schloss JV, Wu JY. Polyhydroxylated C60, fullerenols, as glutamate receptor antagonists and neuroprotective agents. J Neurosci Res. 2000;62:600-7. CrossRef.1002/1097-4547(20001115)62:4<600::AID-JNR15>3.0.CO;2-F
  203.  
  204. Foley S, Crowley C, Smaihi M, Bonfils C, Erlanger BF, Seta P, Larroque C. Cellular localisation of a water-soluble fullerene derivative. Biochem Biophys Res Commun. 2002;294 (1) :116-19. CrossRef.1016/S0006-291X(02)00445-X
  205.  
  206. Cai X, Jia H, Liu Z, Hou B, Luo C, Feng Z, Li W, Liu J. Polyhydroxylated fullerene derivative C60(OH)24 prevents mitochondrial dysfunction and oxidative damage in an MPP+-induced cellular model of Parkinson's disease. J Neurosci Res. 2008;86(16): 3622-34. CrossRef PubMed
  207.  
  208. Prylutskyy YI, Vereshchaka IV, Maznychenko AV, Bulgakova NV, Gonchar OO, Kyzyma OA, Ritter U, Scharff P, Tomiak T, Nozdrenko DM, Mishchenko IV, Kostyukov AI. C60 fullerene as promising therapeutic agent for correcting and preventing skeletal muscle fatigue. J Nanobiotechnol. 2017; 15:8. CrossRef PubMed PubMedCentral
  209.  
  210. Gonchar O., Maznychenko A., Bulgakova N., Vereschaka I., Tomiak T., Ritter U., Prylutskyy Y., Mankovska I., Kostyukov A. C60 Fullerene prevents restraint stressinduced oxidative disorders in rat tissues: possible involvement of the Nrf2/ARE-antioxidant pathway. Oxid Med Cell Long. 2018; 2018 (Article ID 2518676): 17 CrossRef PubMed PubMedCentral
  211.  

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