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Abstract

Parkinson's disease (PD) is a multifaceted neurodegenerative condition marked by the progressive loss of dopaminergic neurons, leading to impairments in movement and cognition. This research offers an in-depth examination of the pathophysiological pathways associated with PD, emphasising the roles of oxidative stress, mitochondrial dysfunction, and neuroinflammation. The study examines the interaction between genetic and environmental factors in the development of PD, highlighting the significance of oxidative stress, mitochondrial dysfunction, and excitotoxicity in the degeneration of dopaminergic neurons. It also looks into the impact of neuroinflammation and microglial activation on the causes of PD. Despite considerable progress in research, there remains a lack of effective treatments that can modify the course of the disease, highlighting the pressing need for new therapeutic approaches that address mitochondrial malfunction, oxidative stress, and neuroinflammation. This study assesses the neuroprotective efficacy of various substances, notably natural agents like resveratrol, curcumin, ginsenoside, and melatonin, for managing PD. Although these natural chemicals show promise, further robust clinical trials are needed to confirm their effectiveness and safety, as well as to investigate their potential incorporation into conventional PD treatment.

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2025-07-28
2025-11-05
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References

  1. Lorraine V. Disease-modifying strategies for Parkinson's disease. Mov Disord. 2015 30 11 1442 10.1002/mds.26354
    [Google Scholar]
  2. Cheng U.C. Ulane C.M. Burke R.E. Clinical progression in Parkinson disease and the neurobiology of axons. Ann Neurol 2010 67 6 715 10.1002/ana.21995
    [Google Scholar]
  3. Anthony H.V. Etiology and pathogenesis of Parkinson disease. Neurol Clin 2009 27 3 583 10.1016/j.ncl.2009.04.004.5
    [Google Scholar]
  4. Braak H. Tredici K.D. Rüb U. de Vos R.A.I. Jansen Steur E.N.H. Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging 2003 24 2 197 211 10.1016/S0197‑4580(02)00065‑9 12498954
    [Google Scholar]
  5. Zeng X.S. Geng W.S. Jia J.J. Neurotoxin-induced animal models of Parkinson disease: Pathogenic mechanism and assessment. ASN Neuro 2018 10 1 1759091418777438 10.1177/1759091418777438 29809058
    [Google Scholar]
  6. Cannon J.R. Greenamyre J.T. The role of environmental exposures in neurodegeneration and neurodegenerative diseases. Toxicol. Sci. 2011 124 2 225 250 10.1093/toxsci/kfr239 21914720
    [Google Scholar]
  7. Martin I. Dawson V.L. Dawson T.M. Recent advances in the genetics of Parkinson’s disease. Annu. Rev. Genomics Hum. Genet. 2011 12 1 301 325 10.1146/annurev‑genom‑082410‑101440 21639795
    [Google Scholar]
  8. Schapira A.H.V. Progress in neuroprotection in Parkinson’s disease. Eur. J. Neurol. 2008 15 s1 Suppl. 1 5 13 10.1111/j.1468‑1331.2008.02055.x 18353131
    [Google Scholar]
  9. Athauda D. Foltynie T. The ongoing pursuit of neuroprotective therapies in Parkinson disease. Nat. Rev. Neurol. 2015 11 1 25 40 10.1038/nrneurol.2014.226 25447485
    [Google Scholar]
  10. Reichmann H. Premotor diagnosis of Parkinson’s disease. Neurosci. Bull. 2017 33 5 526 534 10.1007/s12264‑017‑0159‑5 28776303
    [Google Scholar]
  11. Stocchi F. Olanow C.W. Neuroprotection in Parkinson’s disease: Clinical trials. Ann. Neurol. 2003 53 S3 Suppl. 3 S87 S99 10.1002/ana.10488 12666101
    [Google Scholar]
  12. Olanow C.W. Hauser R.A. Jankovic J. Langston W. Lang A. Poewe W. Tolosa E. Stocchi F. Melamed E. Eyal E. Rascol O. A randomized, double-blind, placebo-controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson’s disease (the ADAGIO study): Rationale, design, and baseline characteristics. Mov. Disord. 2008 23 15 2194 2201 10.1002/mds.22218 18932271
    [Google Scholar]
  13. German D.C. Manaye K.F. Sonsalla P.K. Brooks B.A. Midbrain dopaminergic cell loss in Parkinson’s disease and MPTP-induced parkinsonism: Sparing of calbindin-D28k-containing cells. Ann. N. Y. Acad. Sci. 1992 648 1 42 62 10.1111/j.1749‑6632.1992.tb24523.x 1353337
    [Google Scholar]
  14. Alexander G.E. Biology of Parkinson’s disease: Pathogenesis and pathophysiology of a multisystem neurodegenerative disorder. Dialogues Clin. Neurosci. 2004 6 3 259 280 10.31887/DCNS.2004.6.3/galexander 22033559
    [Google Scholar]
  15. Maiti P. Manna J. Dunbar G.L. Current understanding of the molecular mechanisms in Parkinson’s disease: Targets for potential treatments. Transl. Neurodegener. 2017 6 1 28 10.1186/s40035‑017‑0099‑z 29090092
    [Google Scholar]
  16. Gupta Y.K. Gupta M. Kohli K. Neuroprotective role of melatonin in oxidative stress vulnerable brain. Indian J. Physiol. Pharmacol. 2003 47 4 373 386 15266948
    [Google Scholar]
  17. Guetens G. Boeck G.D. Highley M. van Oosterom A.T. de Bruijn E.A. Oxidative DNA damage: Biological significance and methods of analysis. Crit. Rev. Clin. Lab. Sci. 2002 39 4-5 331 457 10.1080/10408360290795547 12385502
    [Google Scholar]
  18. Skaper S.D. Floreani M. Ceccon M. Facci L. Giusti P. Excitotoxicity, oxidative stress, and the neuroprotective potential of melatonin. Ann. N. Y. Acad. Sci. 1999 890 1 107 118 10.1111/j.1749‑6632.1999.tb07985.x 10668417
    [Google Scholar]
  19. Kim-Han J.S. Antenor-Dorsey J.A. O’Malley K.L. The parkinsonian mimetic, MPP+, specifically impairs mitochondrial transport in dopamine axons. J. Neurosci. 2011 31 19 7212 7221 10.1523/JNEUROSCI.0711‑11.2011 21562285
    [Google Scholar]
  20. Dr Marie-Françoise Chesselet MD Modelling of Parkinson's disease in mice. Lancet Neurol. 2011 10 12 1108 10.1016/S1474‑4422(11)70227‑7
    [Google Scholar]
  21. Wang X. Michaelis E.K. Selective neuronal vulnerability to oxidative stress in the brain. Front. Aging Neurosci. 2010 2 12 10.3389/fnagi.2010.00012 20552050
    [Google Scholar]
  22. Brieger K. Schiavone S. Miller J. Jr Krause K.H. Reactive oxygen species: From health to disease. Swiss Med. Wkly. 2012 142 3334 w13659 10.4414/smw.2012.13659 22903797
    [Google Scholar]
  23. Lee D.H. Gold R. Linker R.A. Mechanisms of oxidative damage in multiple sclerosis and neurodegenerative diseases: Therapeutic modulation via fumaric acid esters. Int. J. Mol. Sci. 2012 13 9 11783 11803 10.3390/ijms130911783 23109883
    [Google Scholar]
  24. Wirdefeldt K. Adami H.O. Cole P. Trichopoulos D. Mandel J. Epidemiology and etiology of Parkinson’s disease: A review of the evidence. Eur. J. Epidemiol. 2011 26 S1 Suppl. 1 1 58 10.1007/s10654‑011‑9581‑6 21626386
    [Google Scholar]
  25. Wakabayashi K. Hayashi S. Yoshimoto M. Kudo H. Takahashi H. NACP/α-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson’s disease brains. Acta Neuropathol. 2000 99 1 14 20 10.1007/PL00007400 10651022
    [Google Scholar]
  26. Klein C. Westenberger A. Genetics of Parkinson’s disease. Cold Spring Harb. Perspect. Med. 2012 2 1 a008888 10.1101/cshperspect.a008888 22315721
    [Google Scholar]
  27. Michel P.P. Hirsch E.C. Hunot S. Understanding dopaminergic cell death pathways in Parkinson disease. Neuron 2016 90 4 675 691 10.1016/j.neuron.2016.03.038 27196972
    [Google Scholar]
  28. Goldenberg M.M. Medical management of Parkinson’s disease. P&T 2008 33 10 590 606 19750042
    [Google Scholar]
  29. Schapira A.H.V. Cooper J.M. Dexter D. Clark J.B. Jenner P. Marsden C.D. Mitochondrial complex I deficiency in Parkinson’s disease. J. Neurochem. 1990 54 3 823 827 10.1111/j.1471‑4159.1990.tb02325.x 2154550
    [Google Scholar]
  30. Gherardi G. Corbioli G. Ruzza F. Rizzuto R. CoQ10 and resveratrol effects to ameliorate aged-related mitochondrial dysfunctions. Nutrients 2022 14 20 4326 10.3390/nu14204326 36297010
    [Google Scholar]
  31. Whitton P.S. Inflammation as a causative factor in the aetiology of Parkinson’s disease. Br. J. Pharmacol. 2007 150 8 963 976 10.1038/sj.bjp.0707167 17339843
    [Google Scholar]
  32. Siracusa R. Scuto M. Fusco R. Trovato A. Ontario M.L. Crea R. Di Paola R. Cuzzocrea S. Calabrese V. Anti-inflammatory and anti-oxidant activity of Hidrox® in rotenone-induced Parkinson’s disease in mice. Antioxidants 2020 9 9 824 10.3390/antiox9090824 32899274
    [Google Scholar]
  33. Lin L.F.H. Doherty D.H. Lile J.D. Bektesh S. Collins F. GDNF: A glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 1993 260 5111 1130 1132 10.1126/science.8493557 8493557
    [Google Scholar]
  34. Penttinen A.M. Parkkinen I. Voutilainen M.H. Koskela M. Bäck S. Their A. Richie C.T. Domanskyi A. Harvey B.K. Tuominen R.K. Nevalaita L. Saarma M. Airavaara M. Pre-α-pro-GDNF and pre-β-pro-GDNF isoforms are neuroprotective in the 6-hydroxydopamine rat model of Parkinson’s disease. Front. Neurol. 2018 9 457 10.3389/fneur.2018.00457 29973907
    [Google Scholar]
  35. Stefanis L. Alpha-synuclein in Parkinson’s disease: A neuropathological review. Brain Pathol. 2012 22 6 747 763
    [Google Scholar]
  36. Hu S. Tan J. Qin L. Lv L. Yan W. Zhang H. Tang B. Wang C. Molecular chaperones and Parkinson’s disease. Neurobiol. Dis. 2021 160 105527 10.1016/j.nbd.2021.105527 34626793
    [Google Scholar]
  37. Surmeier D.J. Guzman J.N. Sanchez-Padilla J. Goldberg J.A. The origins of oxidant stress in Parkinson’s disease and therapeutic strategies. Antioxid. Redox Signal. 2011 14 7 1289 1301 10.1089/ars.2010.3521 20712409
    [Google Scholar]
  38. Liss B. Striessnig J. The potential of L-type calcium channels as a drug target for neuroprotective therapy in Parkinson’s disease. Annu. Rev. Pharmacol. Toxicol. 2019 59 1 263 289 10.1146/annurev‑pharmtox‑010818‑021214 30625283
    [Google Scholar]
  39. Johnson S.L. Park H.Y. DaSilva N.A. Vattem D.A. Ma H. Seeram N.P. Levodopa-reduced Mucuna pruriens seed extract shows neuroprotective effects against Parkinson’s disease in murine microglia and human neuroblastoma cells, Caenorhabditis elegans, and Drosophila melanogaster. Nutrients 2018 10 9 1139 10.3390/nu10091139 30131460
    [Google Scholar]
  40. Cerri S. Blandini F. An update on the use of non-ergot dopamine agonists for the treatment of Parkinson’s disease. Expert Opin. Pharmacother. 2020 21 18 2279 2291 10.1080/14656566.2020.1805432 32804544
    [Google Scholar]
  41. Sarkar S. Raymick J. Imam S. Neuroprotective and therapeutic strategies against Parkinson’s disease: Recent perspectives. Int. J. Mol. Sci. 2016 17 6 904 10.3390/ijms17060904 27338353
    [Google Scholar]
  42. Paudel P. Seong S.H. Wu S. Park S. Jung H.A. Choi J.S. Eckol as a potential therapeutic against neurodegenerative diseases targeting dopamine D3/D4 receptors. Mar. Drugs 2019 17 2 108 10.3390/md17020108 30744179
    [Google Scholar]
  43. Seidl S.E. Potashkin J.A. The promise of neuroprotective agents in Parkinson’s disease. Front. Neurol. 2011 2 68 10.3389/fneur.2011.00068 22125548
    [Google Scholar]
  44. Peplow P.V. Martinez B. Neuroprotection by immunomodulatory agents in animal models of Parkinson’s disease. Neural Regen. Res. 2018 13 9 1493 1506 10.4103/1673‑5374.237108 30127102
    [Google Scholar]
  45. Tan Y.Y. Jenner P. Chen S.D. Monoamine Oxidase-B inhibitors for the treatment of Parkinson’s disease: Past, present, and future. J. Parkinsons Dis. 2022 12 2 477 493 10.3233/JPD‑212976 34957948
    [Google Scholar]
  46. Koh R.Y. Chew Z.X. Lim C.L. Ng K.Y. Chye S.M. Ling A.P.K. The role of monoamine oxidase b inhibitors in the treatment of Parkinson’s disease - An update. CNS Neurol. Disord. Drug Targets 2023 22 3 329 352 10.2174/1871527321666211231100255 34970960
    [Google Scholar]
  47. Alborghetti M. Bianchini E. De Carolis L. Galli S. Pontieri F.E. Rinaldi D. Type-B monoamine oxidase inhibitors in neurological diseases. Neural Regen. Res. 2024 19 1 16 21 10.4103/1673‑5374.375299 37488838
    [Google Scholar]
  48. Nagatsu T. Nakashima A. Monoamine oxidase inhibitor (MAO-I)-mediated neuroprotection for treating Parkinson’s disease. NeuroPsychopharmacotherapy. Springer 2020 1 21 10.1007/978‑3‑319‑56015‑1_238‑2
    [Google Scholar]
  49. Li Y. Liu L. Barger S.W. Mrak R.E. Griffin W.S.T. Vitamin E suppression of microglial activation is neuroprotective. J. Neurosci. Res. 2001 66 2 163 170 10.1002/jnr.1208 11592111
    [Google Scholar]
  50. Roghani M. Behzadi G. Neuroprotective effect of vitamin E on the early model of Parkinson’s disease in rat: Behavioral and histochemical evidence11Published on the World Wide Web 3 January 2001. Brain Res. 2001 892 1 211 217 10.1016/S0006‑8993(00)03296‑0 11172767
    [Google Scholar]
  51. Grünewald R.A. Ascorbic acid in the brain. Brain Res. Brain Res. Rev. 1993 18 1 123 133 10.1016/0165‑0173(93)90010‑W 8467348
    [Google Scholar]
  52. Seidl S.E. Potashkin J.A. The promise of neuroprotective agents in Parkinson’s disease. Front. Neurol. 2011 2 68 10.3389/fneur.2011.00068
    [Google Scholar]
  53. Eyles D.W. Smith S. Kinobe R. Hewison M. McGrath J.J. Distribution of the Vitamin D receptor and 1α-hydroxylase in human brain. J. Chem. Neuroanat. 2005 29 1 21 30 10.1016/j.jchemneu.2004.08.006 15589699
    [Google Scholar]
  54. Wojda U. Salinska E. Kuznicki J. Calcium ions in neuronal degeneration. IUBMB Life 2008 60 9 575 590 10.1002/iub.91 18478527
    [Google Scholar]
  55. Gill S.S. Patel N.K. Hotton G.R. O’Sullivan K. McCarter R. Bunnage M. Brooks D.J. Svendsen C.N. Heywood P. Direct brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease. Nat. Med. 2003 9 5 589 595 10.1038/nm850 12669033
    [Google Scholar]
  56. Orme R.P. Bhangal M.S. Fricker R.A. Calcitriol imparts neuroprotection in vitro to midbrain dopaminergic neurons by upregulating GDNF expression. PLoS One 2013 8 4 e62040 10.1371/journal.pone.0062040 23626767
    [Google Scholar]
  57. Scherzer C.R. Eklund A.C. Morse L.J. Liao Z. Locascio J.J. Fefer D. Schwarzschild M.A. Schlossmacher M.G. Hauser M.A. Vance J.M. Sudarsky L.R. Molecular markers of early Parkinson’s disease based on gene expression in blood. Proc. Nat. Acad. Sci. 2007 104 3 955 60 10.1073/pnas.0610204104
    [Google Scholar]
  58. Manjari S.K.V. Maity S. Poornima R. Yau S.Y. Vaishali K. Stellwagen D. Komal P. Restorative action of vitamin D3 on motor dysfunction through enhancement of neurotrophins and antioxidant expression in the striatum. Neuroscience 2022 492 67 81 10.1016/j.neuroscience.2022.03.039 35413386
    [Google Scholar]
  59. Anderson C. Checkoway H. Franklin G.M. Beresford S. Smith-Weller T. Swanson P.D. Dietary factors in Parkinson’s disease: The role of food groups and specific foods. Mov. Disord. 1999 14 1 21 27 10.1002/1531‑8257(199901)14:1<21::AID‑MDS1006>3.0.CO;2‑Y 9918340
    [Google Scholar]
  60. Dewanjee S Zia-Ul-Haq M Riaz M Sarkhel S Chakraborty P Ahmed S Carotenoids as antiparkinson agents. Carotenoids: Structure and Function in the Human Body. Springer 2021 2021 533 5554 10.1007/978‑3‑030‑46459‑2_15
    [Google Scholar]
  61. Coimbra C.G. Junqueira V.B.C. High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson’s disease patients. Braz. J. Med. Biol. Res. 2003 36 10 1409 1417 10.1590/S0100‑879X2003001000019 14502375
    [Google Scholar]
  62. Murakami K. Miyake Y. Sasaki S. Tanaka K. Fukushima W. Kiyohara C. Tsuboi Y. Yamada T. Oeda T. Miki T. Kawamura N. Sakae N. Fukuyama H. Hirota Y. Nagai M. Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson’s disease: a case–control study in Japan. Br. J. Nutr. 2010 104 5 757 764 10.1017/S0007114510001005 20338075
    [Google Scholar]
  63. Alhebshi A.H. Odawara A. Gotoh M. Suzuki I. Thymoquinone protects cultured hippocampal and human induced pluripotent stem cells-derived neurons against α-synuclein-induced synapse damage. Neurosci. Lett. 2014 570 126 131 10.1016/j.neulet.2013.09.049 24080376
    [Google Scholar]
  64. Alladi P.A. Mahadevan A. Yasha T.C. Raju T.R. Shankar S.K. Muthane U. Absence of age-related changes in nigral dopaminergic neurons of Asian Indians: Relevance to lower incidence of Parkinson’s disease. Neuroscience 2009 159 1 236 245 10.1016/j.neuroscience.2008.11.051 19135503
    [Google Scholar]
  65. Mythri R.B. Veena J. Harish G. Rao S.B.S. Srinivas Bharath M.M. Chronic dietary supplementation with turmeric protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-mediated neurotoxicity in vivo : Implications for Parkinson’s disease. Br. J. Nutr. 2011 106 1 63 72 10.1017/S0007114510005817 21473798
    [Google Scholar]
  66. Adams B.K. Cai J. Armstrong J. Herold M. Lu Y.J. Sun A. Snyder J.P. Liotta D.C. Jones D.P. Shoji M. EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. Anticancer Drugs 2005 16 3 263 275 10.1097/00001813‑200503000‑00005 15711178
    [Google Scholar]
  67. Pan M.H. Huang T.M. Lin J.K. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab. Dispos. 1999 27 4 486 494 10.1016/S0090‑9556(24)15211‑7 10101144
    [Google Scholar]
  68. Mursaleen L. Noble B. Chan S.H.Y. Somavarapu S. Zariwala M.G. N-Acetylcysteine nanocarriers protect against oxidative stress in a cellular model of Parkinson’s disease. Antioxidants 2020 9 7 600 10.3390/antiox9070600 32660079
    [Google Scholar]
  69. Esteves A.R. Silva D.F. Mitochondrial therapeutic approaches in Parkinson’s disease. Mitochondrial Mechanisms of Degeneration and Repair in Parkinson's Disease. Springer 2016 183 205 10.1007/978‑3‑319‑42139‑1_9
    [Google Scholar]
  70. Brasil F.B. de Almeida F.J.S. Luckachaki M.D. Dall’Oglio E.L. de Oliveira M.R. The isothiocyanate sulforaphane prevents mitochondrial impairment and neuroinflammation in the human dopaminergic SH-SY5Y and in the mouse microglial BV2 cells: Role for heme oxygenase-1. Metab. Brain Dis. 2023 38 2 419 435 10.1007/s11011‑022‑00990‑x 35469083
    [Google Scholar]
  71. Lin K.J. Wang T.J. Chen S.D. Lin K.L. Liou C.W. Lan M.Y. Chuang Y.C. Chuang J.H. Wang P.W. Lee J.J. Wang F.S. Lin H.Y. Lin T.K. Two birds one stone: The neuroprotective effect of antidiabetic agents on parkinson disease—focus on sodium-glucose cotransporter 2 (sglt2) inhibitors. Antioxidants 2021 10 12 1935 10.3390/antiox10121935 34943038
    [Google Scholar]
  72. Cereda E. Barichella M. Pedrolli C. Klersy C. Cassani E. Caccialanza R. Pezzoli G. Diabetes and risk of Parkinson’s disease: A systematic review and meta-analysis. Diabetes Care 2011 34 12 2614 2623 10.2337/dc11‑1584 22110170
    [Google Scholar]
  73. Ibrahim M.N. Ramli R. Kutty K.S. Shah S.A. Earlier onset of motor complications in Parkinson’s patients with comorbid diabetes mellitus. Mov. Disord. 2018 33 12 1967 1968 10.1002/mds.27526 30427552
    [Google Scholar]
  74. Brakedal B. Flønes I. Reiter S.F. Torkildsen Ø. Dölle C. Assmus J. Haugarvoll K. Tzoulis C. Glitazone use associated with reduced risk of Parkinson’s disease. Mov. Disord. 2017 32 11 1594 1599 10.1002/mds.27128 28861893
    [Google Scholar]
  75. Cao L. Li D. Feng P. Li L. Xue G.F. Li G. Hölscher C. A novel dual GLP-1 and GIP incretin receptor agonist is neuroprotective in a mouse model of Parkinson’s disease by reducing chronic inflammation in the brain. Neuroreport 2016 27 6 384 391 10.1097/WNR.0000000000000548 26918675
    [Google Scholar]
  76. Valencia W.M. Palacio A. Tamariz L. Florez H. Metformin and ageing: Improving ageing outcomes beyond glycaemic control. Diabetologia 2017 60 9 1630 1638 10.1007/s00125‑017‑4349‑5 28770328
    [Google Scholar]
  77. Lin Y. Wang K. Ma C. Wang X. Gong Z. Zhang R. Zang D. Cheng Y. Evaluation of metformin on cognitive improvement in patients with non-dementia vascular cognitive impairment and abnormal glucose metabolism. Front. Aging Neurosci. 2018 10 227 10.3389/fnagi.2018.00227 30100873
    [Google Scholar]
  78. Rotermund C. Machetanz G. Fitzgerald J.C. The therapeutic potential of metformin in neurodegenerative diseases. Front. Endocrinol. 2018 9 400 10.3389/fendo.2018.00400 30072954
    [Google Scholar]
  79. Lu M. Su C. Qiao C. Bian Y. Ding J. Hu G. Metformin prevents dopaminergic neuron death in MPTP/P-induced mouse model of Parkinson’s disease via autophagy and mitochondrial ROS clearance. Int. J. Neuropsychopharmacol. 2016 19 9 pyw047 10.1093/ijnp/pyw047 27207919
    [Google Scholar]
  80. Alrouji M. Al-Kuraishy H.M. Al-Gareeb A.I. Saad H.M. Batiha G.E.S. A story of the potential effect of non-steroidal anti-inflammatory drugs (NSAIDs) in Parkinson’s disease: Beneficial or detrimental effects. Inflammopharmacology 2023 31 2 673 688 10.1007/s10787‑023‑01192‑2 36961665
    [Google Scholar]
  81. Junrong H.E. Zai L.I. Xipei C.H. Neuroprotective effect of ibuprofen on ischemic stroke rats and its effect on Nrf2/SLC7A1I/GPX4 signal pathway. J. Practical Medicine. 2023 39 5 10.3969/j.issn.1006‑5725.2023.15.006
    [Google Scholar]
  82. Finsterer J. Almeida A.C.G. Chaddad-Neto F. Scorza F.A. Statin therapy in Parkinson’s disease cuts mortality. Parkinsonism Relat. Disord. 2024 126 106043 10.1016/j.parkreldis.2024.106043 38461038
    [Google Scholar]
  83. Bhardwaj R. Deshmukh R. Neurotrophic factors and Parkinson’s disease. Clin. Investig. 2018 7 4 53 62
    [Google Scholar]
  84. Carrillo-Mora P. Silva-Adaya D. Villaseñor-Aguayo K. Glutamate in Parkinson’s disease: Role of antiglutamatergic drugs. Basal Ganglia 2013 3 3 147 157 10.1016/j.baga.2013.09.001
    [Google Scholar]
  85. Lin J. Pang D. Li C. Ou R. Yu Y. Cui Y. Huang J. Shang H. Calcium channel blockers and Parkinson’s disease: A systematic review and meta-analysis. Ther. Adv. Neurol. Disord. 2024 17 17562864241252713 10.1177/17562864241252713 38770432
    [Google Scholar]
  86. Wang Q.M. Xu Y.Y. Liu S. Ma Z.G. Isradipine attenuates MPTP-induced dopamine neuron degeneration by inhibiting up-regulation of L-type calcium channels and iron accumulation in the substantia nigra of mice. Oncotarget 2017 8 29 47284 47295 10.18632/oncotarget.17618 28521299
    [Google Scholar]
  87. Zeng X. An H. Yu F. Wang K. Zheng L. Zhou W. Bao Y. Yang J. Shen N. Huang D. Benefits of iron chelators in the treatment of Parkinson’s disease. Neurochem. Res. 2021 46 5 1239 1251 10.1007/s11064‑021‑03262‑9 33646533
    [Google Scholar]
  88. Yang L. Calingasan N.Y. Wille E.J. Cormier K. Smith K. Ferrante R.J. Flint Beal M. Combination therapy with Coenzyme Q 10 and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s diseases. J. Neurochem. 2009 109 5 1427 1439 10.1111/j.1471‑4159.2009.06074.x 19476553
    [Google Scholar]
  89. Sääksjärvi K. Knekt P. Rissanen H. Laaksonen M.A. Reunanen A. Männistö S. Prospective study of coffee consumption and risk of Parkinson’s disease. Eur. J. Clin. Nutr. 2008 62 7 908 915 10.1038/sj.ejcn.1602788 17522612
    [Google Scholar]
  90. Kachroo A. Irizarry M.C. Schwarzschild M.A. Caffeine protects against combined paraquat and maneb-induced dopaminergic neuron degeneration. Exp. Neurol. 2010 223 2 657 661 10.1016/j.expneurol.2010.02.007 20188092
    [Google Scholar]
  91. Joghataie M.T. Roghani M. Negahdar F. Hashemi L. Protective effect of caffeine against neurodegeneration in a model of Parkinson’s disease in rat: Behavioral and histochemical evidence. Parkinsonism Relat. Disord. 2004 10 8 465 468 10.1016/j.parkreldis.2004.06.004 15542005
    [Google Scholar]
  92. Aguiar L.M.V. Nobre H.V. Jr Macêdo D.S. Oliveira A.A. Freitas R.M. Vasconcelos S.M. Cunha G.M.A. Sousa F.C.F. Viana G.S.B. Neuroprotective effects of caffeine in the model of 6-hydroxydopamine lesion in rats. Pharmacol. Biochem. Behav. 2006 84 3 415 419 10.1016/j.pbb.2006.05.027 16844208
    [Google Scholar]
  93. Xu K. Xu Y.H. Chen J.F. Schwarzschild M.A. Neuroprotection by caffeine: Time course and role of its metabolites in the MPTP model of Parkinson’s disease. Neuroscience 2010 167 2 475 481 10.1016/j.neuroscience.2010.02.020 20167258
    [Google Scholar]
  94. Xu K. Xu Y.H. Chen J.F. Schwarzschild M.A. Caffeine’s neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity shows no tolerance to chronic caffeine administration in mice. Neurosci. Lett. 2002 322 1 13 16 10.1016/S0304‑3940(02)00069‑1 11958832
    [Google Scholar]
  95. Russo M. Spagnuolo C. Tedesco I. Bilotto S. Russo G.L. The flavonoid quercetin in disease prevention and therapy: Facts and fancies. Biochem. Pharmacol. 2012 83 1 6 15 10.1016/j.bcp.2011.08.010 21856292
    [Google Scholar]
  96. Russo M. Spagnuolo C. Tedesco I. Bilotto S. Russo G.L. Protective effects of red onion (Allium cepa) ethanolic extract on learning and memory impairments in animal models of diabetes. Biochem. Pharmacol. 2017 6 3 e909 10.22086/gmj.v0i0.909
    [Google Scholar]
  97. Hegazy E.M. Sabry A. Khalil W.K.B. Neuroprotective effects of onion and garlic root extracts against Alzheimer’s disease in rats: Antimicrobial, histopathological, and molecular studies. BioTechnologia 2022 103 2 153 167 10.5114/bta.2022.116210 36606073
    [Google Scholar]
  98. Hwang I.K. Lee C.H. Yoo K.Y. Choi J.H. Park O.K. Lim S.S. Kang I.J. Kwon D.Y. Park J. Yi J.S. Bae Y.S. Won M.H. Neuroprotective effects of onion extract and quercetin against ischemic neuronal damage in the gerbil hippocampus. J. Med. Food 2009 12 5 990 995 10.1089/jmf.2008.1400 19857061
    [Google Scholar]
  99. Ashfaq F. Ali Q. Haider M.A. Hafeez M.M. Malik A. Therapeutic activities of garlic constituent phytochemicals. Biol. Clin. Sci. Res. J 2021 2021 1 10.54112/bcsrj.v2021i1.53
    [Google Scholar]
  100. Bigham M. Mohammadipour A. Hosseini M. Malvandi A.M. Ebrahimzadeh-Bideskan A. Neuroprotective effects of garlic extract on dopaminergic neurons of substantia nigra in a rat model of Parkinson’s disease: Motor and non-motor outcomes. Metab. Brain Dis. 2021 36 5 927 937 10.1007/s11011‑021‑00705‑8 33656625
    [Google Scholar]
  101. Medalcho T.H. Abegaz K. Dessalegn E. Mate J. Aflatoxin B1 detoxification potentials of garlic, ginger, cardamom, black cumin, and sautéing in ground spice mix red pepper products. Toxins 2023 15 5 307 10.3390/toxins15050307 37235342
    [Google Scholar]
  102. Abdel-Wahhab M.A. Aly S.E. Antioxidants and radical scavenging properties of vegetable extracts in rats fed aflatoxin-contaminated diet. J. Agric. Food Chem. 2003 51 8 2409 2414 10.1021/jf0209185 12670189
    [Google Scholar]
  103. Iftikhar A. Nausheen R. Muzaffar H. Naeem M.A. Farooq M. Khurshid M. Almatroudi A. Alrumaihi F. Allemailem K.S. Anwar H. Potential therapeutic benefits of honey in neurological disorders: The role of polyphenols. Molecules 2022 27 10 3297 10.3390/molecules27103297 35630774
    [Google Scholar]
  104. Topal N. Bulduk I. Mut Z. Bozodlu H. Tosun Y.K. Flowers, pollen and honey for use in the treatment of Parkinson’s disease. Revista de Chimie 2020 71 9 308 319 10.37358/RC.20.9.8341
    [Google Scholar]
  105. Ara G. Afzal M. Jyoti S. Naz F. Rahul Siddique Y.H. Effect of Myricetin on the loss of dopaminergic neurons in the transgenic Drosophila model of Parkinson’s disease. Curr. Drug Ther. 2019 14 1 58 64 10.2174/1574885513666180529114546
    [Google Scholar]
  106. Huang B. Liu J. Ma D. Chen G. Wang W. Fu S. Myricetin prevents dopaminergic neurons from undergoing neuroinflammation-mediated degeneration in a lipopolysaccharide-induced Parkinson’s disease model. J. Funct. Foods 2018 45 452 461 10.1016/j.jff.2018.04.018
    [Google Scholar]
  107. Guo B. Zheng C. Cai W. Cheng J. Wang H. Li H. Sun Y. Cui W. Wang Y. Han Y. Lee S.M.Y. Zhang Z. Multifunction of chrysin in Parkinson’s model: Anti-neuronal apoptosis, neuroprotection via activation of MEF2D, and inhibition of monoamine oxidase-B. J. Agric. Food Chem. 2016 64 26 5324 5333 10.1021/acs.jafc.6b01707 27245668
    [Google Scholar]
  108. Ascherio A. LeWitt P.A. Xu K. Eberly S. Watts A. Matson W.R. Marras C. Kieburtz K. Rudolph A. Bogdanov M.B. Schwid S.R. Tennis M. Tanner C.M. Beal M.F. Lang A.E. Oakes D. Fahn S. Shoulson I. Schwarzschild M.A. Urate as a predictor of the rate of clinical decline in Parkinson disease. Arch. Neurol. 2009 66 12 1460 1468 10.1001/archneurol.2009.247 19822770
    [Google Scholar]
  109. Yu Z.F. Bruce-Keller A.J. Goodman Y. Mattson M.P. Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo. J. Neurosci. Res. 1998 53 5 613 625 10.1002/(SICI)1097‑4547(19980901)53:5<613::AID‑JNR11>3.0.CO;2‑1 9726432
    [Google Scholar]
  110. Xie Y. Zeng H. Huang Z. Xu H. Fan Q. Zhang Y. Zheng B. Effect of maternal administration of edible bird’s nest on the learning and memory abilities of suckling offspring in mice. Neural Plast. 2018 2018 1 13 10.1155/2018/7697261 29765403
    [Google Scholar]
  111. Tai S.K. Koh R.Y. Ng K.Y. Chye S.M. A mini review on medicinal effects of edible bird’s nest. Lett. Health Biol. Sci. 2017 2 1 65 67
    [Google Scholar]
  112. Miranda M. Morici J.F. Zanoni M.B. Bekinschtein P. Brain-derived neurotrophic factor: A key molecule for memory in the healthy and the pathological brain. Front. Cell. Neurosci. 2019 13 363 10.3389/fncel.2019.00363 31440144
    [Google Scholar]
  113. Loh S.P. Cheng S.H. Mohamed W. Edible bird’s nest as a potential cognitive enhancer. Front. Neurol. 2022 13 865671 10.3389/fneur.2022.865671 35599726
    [Google Scholar]
  114. Hou Z. He P. Imam M.U. Qi J. Tang S. Song C. Ismail M. Edible bird’s nest prevents menopause-related memory and cognitive decline in rats via increased hippocampal sirtuin-1 expression. Oxid. Med. Cell. Longev. 2017 2017 1 7205082 10.1155/2017/7205082 29104731
    [Google Scholar]
  115. Qidwai W. Hamza H.B. Qureshi R. Gilani A. Effectiveness, safety, and tolerability of powdered Nigella sativa (kalonji) seed in capsules on serum lipid levels, blood sugar, blood pressure, and body weight in adults: Results of a randomized, double-blind controlled trial. J. Altern. Complement. Med. 2009 15 6 639 644 10.1089/acm.2008.0367 19500003
    [Google Scholar]
  116. Tuo Q. Zou J. Lei P. Rodent models of vascular cognitive impairment. J. Mol. Neurosci. 2021 71 5 1 12 10.1007/s12031‑020‑01733‑2 33107013
    [Google Scholar]
  117. Ahmad A. Husain A. Mujeeb M. Khan S.A. Najmi A.K. Siddique N.A. Damanhouri Z.A. Anwar F. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac. J. Trop. Biomed. 2013 3 5 337 352 10.1016/S2221‑1691(13)60075‑1 23646296
    [Google Scholar]
  118. Hosseinian S. Rad A.K. Bideskan A.E. Soukhtanloo M. Sadeghnia H. Shafei M.N. Motejadded F. Mohebbati R. Shahraki S. Beheshti F. Thymoquinone ameliorates renal damage in unilateral ureteral obstruction in rats. Pharmacol. Rep. 2017 69 4 648 657 10.1016/j.pharep.2017.03.002 28521173
    [Google Scholar]
  119. Ebrahimi S.S. Oryan S. Izadpanah E. Hassanzadeh K. Thymoquinone exerts neuroprotective effect in animal model of Parkinson’s disease. Toxicol. Lett. 2017 276 108 114 10.1016/j.toxlet.2017.05.018 28526446
    [Google Scholar]
  120. Ghosh S. Banerjee S. Sil P.C. The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update. Food Chem. Toxicol. 2015 83 111 124 10.1016/j.fct.2015.05.022 26066364
    [Google Scholar]
  121. Nebrisi E.E. Neuroprotective activities of curcumin in Parkinson’s disease: A review of the literature. Int. J. Mol. Sci. 2021 22 20 11248 10.3390/ijms222011248 34681908
    [Google Scholar]
  122. Renaud J. Martinoli M.G. Resveratrol as a protective molecule for neuroinflammation: A review of mechanisms. Curr. Pharm. Biotechnol. 2014 15 4 318 329 10.2174/1389201015666140617101332 24938890
    [Google Scholar]
  123. Chao J. Li H. Cheng K.W. Yu M.S. Chang R.C.C. Wang M. Protective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. J. Nutr. Biochem. 2010 21 6 482 489 10.1016/j.jnutbio.2009.02.004 19443200
    [Google Scholar]
  124. Jin F. Wu Q. Lu Y.F. Gong Q.H. Shi J.S. Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson’s disease in rats. Eur. J. Pharmacol. 2008 600 1-3 78 82 10.1016/j.ejphar.2008.10.005 18940189
    [Google Scholar]
  125. Okawara M. Katsuki H. Kurimoto E. Shibata H. Kume T. Akaike A. Resveratrol protects dopaminergic neurons in midbrain slice culture from multiple insults. Biochem. Pharmacol. 2007 73 4 550 560 10.1016/j.bcp.2006.11.003 17147953
    [Google Scholar]
  126. Lee K.W. Jung S.Y. Choi S.M. Yang E.J. Effects of ginsenoside Re on LPS-induced inflammatory mediators in BV2 microglial cells. BMC Complement. Altern. Med. 2012 12 1 196 10.1186/1472‑6882‑12‑196 23102375
    [Google Scholar]
  127. Kim H.J. Kim P. Shin C.Y. A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system. J. Ginseng Res. 2013 37 1 8 29 10.5142/jgr.2013.37.8 23717153
    [Google Scholar]
  128. Xu B.B. Liu C.Q. Gao X. Zhang W.Q. Wang S.W. Cao Y.L. Possible mechanisms of the protection of ginsenoside Re against MPTP-induced apoptosis in substantia nigra neurons of Parkinson’s disease mouse model. J. Asian Nat. Prod. Res. 2005 7 3 215 224 10.1080/10286020410001690172 15621629
    [Google Scholar]
  129. Hardeland R. Investigational melatonin receptor agonists. Expert Opin. Investig. Drugs 2010 19 6 747 764 10.1517/13543784.2010.482926 20408738
    [Google Scholar]
  130. Tan D.X. Manchester L.C. Terron M.P. Flores L.J. Reiter R.J. One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species? J. Pineal Res. 2007 42 1 28 42 10.1111/j.1600‑079X.2006.00407.x 17198536
    [Google Scholar]
  131. Natesan A.K. Thesis Molecular analysis of melatonin receptors in the chick central nervous system: Role for multiple receptor subtypes. Texas A&M University 2001
    [Google Scholar]
  132. Carrillo-Vico A. Lardone P. Álvarez-Sánchez N. Rodríguez-Rodríguez A. Guerrero J. Melatonin: Buffering the immune system. Int. J. Mol. Sci. 2013 14 4 8638 8683 10.3390/ijms14048638 23609496
    [Google Scholar]
  133. Meng X. Li Y. Li S. Zhou Y. Gan R.Y. Xu D.P. Li H.B. Dietary sources and bioactivities of melatonin. Nutrients 2017 9 4 367 10.3390/nu9040367 28387721
    [Google Scholar]
  134. Arendt J Aulinas A Physiology of the Pineal Gland and Melatonin. South Dartmouth (MA) MDText.com, Inc.
    [Google Scholar]
  135. Koh P.O. Melatonin regulates the calcium-buffering proteins, parvalbumin and hippocalcin, in ischemic brain injury. J. Pineal Res. 2012 53 4 358 365 10.1111/j.1600‑079X.2012.01005.x 22639951
    [Google Scholar]
  136. Li H. Guo Y. Lan Z. Zhang Z. Ahammed G.J. Chang J. Zhang Y. Wei C. Zhang X. Melatonin antagonizes ABA action to promote seed germination by regulating Ca2+ efflux and H2O2 accumulation. Plant Sci. 2021 303 110761 10.1016/j.plantsci.2020.110761 33487347
    [Google Scholar]
  137. Patiño P. Parada E. Farré-Alins V. Molz S. Cacabelos R. Marco-Contelles J. López M.G. Tasca C.I. Ramos E. Romero A. Egea J. Melatonin protects against oxygen and glucose deprivation by decreasing extracellular glutamate and Nox-derived ROS in rat hippocampal slices. Neurotoxicology 2016 57 61 68 10.1016/j.neuro.2016.09.002 27620136
    [Google Scholar]
  138. Lee M.Y. Kuan Y.H. Chen H.Y. Chen T.Y. Chen S.T. Huang C.C. Yang I.P. Hsu Y.S. Wu T.S. Lee E.J. Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats. J. Pineal Res. 2007 42 3 297 309 10.1111/j.1600‑079X.2007.00420.x 17349029
    [Google Scholar]
  139. Jiménez-Delgado A. Ortiz G.G. Delgado-Lara D.L. González-Usigli H.A. González-Ortiz L.J. Cid-Hernández M. Cruz-Serrano J.A. Pacheco-Moisés F.P. Effect of melatonin administration on mitochondrial activity and oxidative stress markers in patients with Parkinson’s disease. Oxid. Med. Cell. Longev. 2021 2021 1 5577541 10.1155/2021/5577541 34707777
    [Google Scholar]
  140. Allaith A.A.A. Antioxidant activity of Bahraini date palm ( Phoenix dactylifera L.) fruit of various cultivars. Int. J. Food Sci. Technol. 2008 43 6 1033 1040 10.1111/j.1365‑2621.2007.01558.x
    [Google Scholar]
  141. Biglari F. AlKarkhi A.F.M. Easa A.M. Antioxidant activity and phenolic content of various date palm (Phoenix dactylifera) fruits from Iran. Food Chem. 2008 107 4 1636 1641 10.1016/j.foodchem.2007.10.033
    [Google Scholar]
  142. Rahmani A.H. Aly S.M. Ali H. Babiker A.Y. Srikar S. Khan A.A. Therapeutic effects of date fruits (Phoenix dactylifera) in the prevention of diseases via modulation of anti-inflammatory, anti-oxidant and anti-tumour activity. Int. J. Clin. Exp. Med. 2014 7 3 483 491 24753740
    [Google Scholar]
  143. Essa M.M. Braidy N. Awlad-Thani K. Vaishnav R. Al-Asmi A. Guillemin G.J. Al-Adawi S. Subash S. Diet rich in date palm fruits improves memory, learning and reduces beta amyloid in transgenic mouse model of Alzheimer′s disease. J. Ayurveda Integr. Med. 2015 6 2 111 120 10.4103/0975‑9476.159073 26167001
    [Google Scholar]
  144. Yusuf A.O. Buraimoh A.A. Agbon A.N. Raji K.B. Akpulu P.S. Preliminary histological studies on the effect of aqueous fruit extract of Phoenix dactylifera L.(date palm) on lead acetate-induced cerebellar damages in Wistar rats. Afr. J. Cell. Pathol. 2017 8 1 1 8 10.5897/AJCPATH17.001
    [Google Scholar]
  145. Subash S. Essa M.M. Al-Asmi A. Al-Adawi S. Vaishnav R. Guillemin G.J. Effect of dietary supplementation of dates in Alzheimer’s disease APPsw/2576 transgenic mice on oxidative stress and antioxidant status. Nutr. Neurosci. 2015 18 6 281 288 10.1179/1476830514Y.0000000134 24954036
    [Google Scholar]
  146. Rai S.N. Singh P. Varshney R. Natural L-DOPA from Mucuna pruriens: A sustainable therapy for Parkinson’s disease. Neurol. Sci. 2023 44 2 621 634 10.1007/s10072‑022‑06493‑y 36301361
    [Google Scholar]
  147. Thakur A.K. Rai G. Mucuna pruriens in Parkinson’s disease: Translational opportunities. CNS Neurol. Disord. Drug Targets 2021 20 5 416 429 10.2174/1871527320666210118105418
    [Google Scholar]
  148. Patel V.K. Yadav S.K. Singh S. Mucuna pruriens enhances striatal dopamine release and motor coordination in MPTP-lesioned mice. J. Ethnopharmacol. 2022 284 114788 10.1016/j.jep.2021.114788
    [Google Scholar]
  149. Wang Y. Li S. Chen L. Ursolic acid attenuates neuroinflammation in MPTP mice by regulating microglial polarization via the PPARγ/NF-κB pathway. Brain Res. Bull. 2023 194 1 10 10.1016/j.brainresbull.2023.01.008
    [Google Scholar]
  150. Javed H. Vaibhav K. Khan M.M. Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced Parkinson’s disease mouse model. Chem. Biol. Interact. 2021 277 91 100 10.1016/j.cbi.2021.03.026
    [Google Scholar]
  151. Kim S.R. Jeong H.Y. Yang S. Ursolic acid suppresses neuroinflammation in MPTP-induced Parkinson’s disease mice via Nrf2/HO-1 signaling. Int. J. Mol. Sci. 2022 23 15 8179 10.3390/ijms23158179 35897755
    [Google Scholar]
  152. Hwang C.J. Kim Y.E. Son D.J. Chlorogenic acid rescues mitochondrial dysfunction in Parkinson’s disease models via PGC-1α upregulation. Antioxidants 2023 12 3 512 10.3390/antiox12030512
    [Google Scholar]
  153. Lee J.E. Song H.S. Park J.H. Chlorogenic acid ameliorates MPTP-induced neurotoxicity and motor deficits in mice by suppressing oxidative stress. Biomol. Ther. 2021 29 3 302 310 10.4062/biomolther.2020.154 33619237
    [Google Scholar]
  154. Bollimpelli V.S. Kumar P. Kondapi A.K. Neuroprotective effect of chlorogenic acid in MPTP-induced Parkinson’s disease mice. Neurochem. Int. 2022 158 105385 10.1016/j.neuint.2022.105385
    [Google Scholar]
  155. Singh M. Murthy V. Ramassamy C. Standardized Withania somnifera extract inhibits apoptosis in Maneb-Paraquat-induced Parkinson’s disease models. Neurotox. Res. 2022 40 3 714 727 10.1007/s12640‑022‑00503‑9 35486353
    [Google Scholar]
  156. Kuboyama T. Tohda C. Komatsu K. Withanoside IV and its active metabolite, sominone, attenuate Aβ(25-35)-induced neurodegeneration. Eur. J. Neurosci. 2020 27 3 647 658 10.1111/j.1460‑9568.2008.06024.x 16553605
    [Google Scholar]
  157. Sharma A. Kumar A. Taliyan R. Synergistic neuroprotection by Withania somnifera and coenzyme Q10 in a Parkinson’s disease model: Role of mitochondrial biogenesis. Phytomedicine 2023 112 154709 10.1016/j.phymed.2023.154709
    [Google Scholar]
  158. Beal M.F. Oakes D. Shoulson I. Henchcliffe C. Galpern W.R. Haas R. Juncos J.L. Nutt J.G. Voss T.S. Ravina B. Shults C.M. Helles K. Snively V. Lew M.F. Griebner B. Watts A. Gao S. Pourcher E. Bond L. Kompoliti K. Agarwal P. Sia C. Jog M. Cole L. Sultana M. Kurlan R. Richard I. Deeley C. Waters C.H. Figueroa A. Arkun A. Brodsky M. Ondo W.G. Hunter C.B. Jimenez-Shahed J. Palao A. Miyasaki J.M. So J. Tetrud J. Reys L. Smith K. Singer C. Blenke A. Russell D.S. Cotto C. Friedman J.H. Lannon M. Zhang L. Drasby E. Kumar R. Subramanian T. Ford D.S. Grimes D.A. Cote D. Conway J. Siderowf A.D. Evatt M.L. Sommerfeld B. Lieberman A.N. Okun M.S. Rodriguez R.L. Merritt S. Swartz C.L. Martin W.R.W. King P. Stover N. Guthrie S. Watts R.L. Ahmed A. Fernandez H.H. Winters A. Mari Z. Dawson T.M. Dunlop B. Feigin A.S. Shannon B. Nirenberg M.J. Ogg M. Ellias S.A. Thomas C.A. Frei K. Bodis-Wollner I. Glazman S. Mayer T. Hauser R.A. Pahwa R. Langhammer A. Ranawaya R. Derwent L. Sethi K.D. Farrow B. Prakash R. Litvan I. Robinson A. Sahay A. Gartner M. Hinson V.K. Markind S. Pelikan M. Perlmutter J.S. Hartlein J. Molho E. Evans S. Adler C.H. Duffy A. Lind M. Elmer L. Davis K. Spears J. Wilson S. Leehey M.A. Hermanowicz N. Niswonger S. Shill H.A. Obradov S. Rajput A. Cowper M. Lessig S. Song D. Fontaine D. Zadikoff C. Williams K. Blindauer K.A. Bergholte J. Propsom C.S. Stacy M.A. Field J. Mihaila D. Chilton M. Uc E.Y. Sieren J. Simon D.K. Kraics L. Silver A. Boyd J.T. Hamill R.W. Ingvoldstad C. Young J. Thomas K. Kostyk S.K. Wojcieszek J. Pfeiffer R.F. Panisset M. Beland M. Reich S.G. Cines M. Zappala N. Rivest J. Zweig R. Lumina L.P. Hilliard C.L. Grill S. Kellermann M. Tuite P. Rolandelli S. Kang U.J. Young J. Rao J. Cook M.M. Severt L. Boyar K. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: No evidence of benefit. JAMA Neurol. 2014 71 5 543 552 10.1001/jamaneurol.2014.131 24664227
    [Google Scholar]
  159. Kieburtz K. Tilley B.C. Elm J.J. Babcock D. Hauser R. Ross G.W. Augustine A.H. Augustine E.U. Aminoff M.J. Bodis-Wollner I.G. Boyd J. Cambi F. Chou K. Christine C.W. Cines M. Dahodwala N. Derwent L. Dewey R.B. Jr Hawthorne K. Houghton D.J. Kamp C. Leehey M. Lew M.F. Liang G.S.L. Luo S.T. Mari Z. Morgan J.C. Parashos S. Pérez A. Petrovitch H. Rajan S. Reichwein S. Roth J.T. Schneider J.S. Shannon K.M. Simon D.K. Simuni T. Singer C. Sudarsky L. Tanner C.M. Umeh C.C. Williams K. Wills A.M. Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: A randomized clinical trial. JAMA 2015 313 6 584 593 10.1001/jama.2015.120 25668262
    [Google Scholar]
  160. Mullin S. Smith L. Lee K. D’Souza G. Woodgate P. Elflein J. Hällqvist J. Toffoli M. Streeter A. Hosking J. Heywood W.E. Khengar R. Campbell P. Hehir J. Cable S. Mills K. Zetterberg H. Limousin P. Libri V. Foltynie T. Schapira A.H.V. Ambroxol for the treatment of patients with Parkinson disease with and without glucocerebrosidase gene mutations: A nonrandomized, noncontrolled trial. JAMA Neurol. 2020 77 4 427 434 10.1001/jamaneurol.2019.4611 31930374
    [Google Scholar]
  161. Dawson T.M. Ko H.S. Dawson V.L. Genetic animal models of Parkinson’s disease. Neuron 2010 66 5 646 661 10.1016/j.neuron.2010.04.034 20547124
    [Google Scholar]
  162. Olanow C.W. Schapira A.H.V. Therapeutic prospects for Parkinson disease. Ann. Neurol. 2013 74 3 337 347 10.1002/ana.24011 24038341
    [Google Scholar]
  163. Puschmann A. Brighina L. Markopoulou K. Aasly J. Chung S.J. Frigerio R. Hadjigeorgiou G. Kõks S. Krüger R. Siuda J. Wider C. Zesiewicz T.A. Maraganore D.M. Clinically meaningful parameters of progression and long-term outcome of Parkinson disease: An international consensus statement. Parkinsonism Relat. Disord. 2015 21 7 675 682 10.1016/j.parkreldis.2015.04.029 25952959
    [Google Scholar]
  164. Pardridge W.M. The blood-brain barrier: Bottleneck in brain drug development. NeuroRx 2005 2 1 3 14 10.1602/neurorx.2.1.3 15717053
    [Google Scholar]
  165. Ayub A. Wettig S. An overview of nanotechnologies for drug delivery to the brain. Pharmaceutics 2022 14 2 224 10.3390/pharmaceutics14020224 35213957
    [Google Scholar]
  166. Nguyen T.T. Dung Nguyen T.T. Vo T.K. Tran N.M.A. Nguyen M.K. Van Vo T. Van Vo G. Nanotechnology-based drug delivery for central nervous system disorders. Biomed. Pharmacother. 2021 143 112117 10.1016/j.biopha.2021.112117 34479020
    [Google Scholar]
  167. Dawson D.A. Wadsworth G. Palmer A.M. A comparative assessment of the efficacy and side-effect liability of neuroprotective compounds in experimental stroke. Brain Res. 2001 892 2 344 350 10.1016/S0006‑8993(00)03269‑8 11172782
    [Google Scholar]
  168. Kalyanaraman B. Teaching the basics of repurposing mitochondria-targeted drugs: From Parkinson’s disease to cancer and back to Parkinson’s disease. Redox Biol. 2020 36 101665 10.1016/j.redox.2020.101665 32795938
    [Google Scholar]
  169. Prediger R.D.S. Effects of caffeine in Parkinson’s disease: From neuroprotection to the management of motor and non-motor symptoms. J. Alzheimers Dis. 2010 20 s1 S205 S220 10.3233/JAD‑2010‑091459
    [Google Scholar]
  170. Griñán-Ferré C. Bellver-Sanchis A. Guerrero A. Pallàs M. Advancing personalized medicine in neurodegenerative diseases: The role of epigenetics and pharmacoepigenomics in pharmacotherapy. Pharmacol. Res. 2024 205 107247 10.1016/j.phrs.2024.107247 38834164
    [Google Scholar]
  171. Pandey S. Jirásko M. Lochman J. Chvátal A. Chottova Dvorakova M. Kučera R. iPSCs in neurodegenerative disorders: A unique platform for clinical research and personalized medicine. J. Pers. Med. 2022 12 9 1485 10.3390/jpm12091485 36143270
    [Google Scholar]
  172. Strianese O. Rizzo F. Ciccarelli M. Galasso G. D’Agostino Y. Salvati A. Del Giudice C. Tesorio P. Rusciano M.R. Precision and personalized medicine: How genomic approach improves the management of cardiovascular and neurodegenerative disease. Genes 2020 11 7 747 10.3390/genes11070747 32640513
    [Google Scholar]
  173. Gouda N.A. Elkamhawy A. Cho J. Emerging therapeutic strategies for Parkinson’s disease and future prospects: A 2021 update. Biomedicines 2022 10 2 371 10.3390/biomedicines10020371 35203580
    [Google Scholar]
  174. Valera E. Masliah E. Combination therapies: The next logical Step for the treatment of synucleinopathies? Mov Disord. 2016 31 2 225 10.1002/mds.26428
    [Google Scholar]
  175. Matsunaga S. Kishi T. Iwata N. Combination therapy with Zonisamide and Antiparkinson drugs for Parkinson’s disease: A meta-analysis. J Alzheimers Dis. 2017 56 4 1229 10.3233/JAD‑161068
    [Google Scholar]
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