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The vicious circle between homocysteine, methyl group-donating vitamins and chronic levodopa intake in Parkinson’s disease

  • Neurology and Preclinical Neurological Studies - Review Article
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Abstract

A biomarker for declined methylation capacity is elevation of homocysteine levels. They increase the risk for onset of vascular disease and contribute to progression of chronic neurodegeneration and aging. This narrative review discusses associations between homocysteine, consumption of methyl group-donating vitamins and impact on disease-generating mechanisms in levodopa-treated patients with Parkinson’s disease. We conclude to recommend levodopa-treated patients to substitute themselves with methyl group-donating vitamins. This is harmless in terms of application of folic acid, methylcobalamin or hydroxocobalamin. Moreover, we suggest a crucial discussion on the value of the various popular hypotheses on Parkinson’s disease-generating mechanisms. Findings from studies with acute levodopa exposure describe oxidative stress generation and impaired methylation capacity, which causes gene dysfunction. Their repeated occurrences contribute to onset of mitochondrial dysfunction, iron enrichment and pathologic protein accumulation in the long term. Current research underestimates these epigenetic, metabolic consequences of chronic levodopa application. Supplementary treatment strategies are recommended to avoid levodopa-related side effects.

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References

  • Ahlskog JE (2023) Levodopa, homocysteine and Parkinson’s disease: What’s the problem? Parkinsonism Relat Disord 109:105357

    Article  PubMed  Google Scholar 

  • Antonini A, Bondiolotti G, Natuzzi F, Bareggi SR (2010) Levodopa and 3-OMD levels in Parkinson patients treated with Duodopa. Eur Neuropsychopharmacol 20:683–687

    Article  CAS  PubMed  Google Scholar 

  • Ben Shlomo Y, Marmot MG (1995) Survival and cause of death in a cohort of patients with parkinsonism: possible clues to aetiology? J Neurol Neurosurg Psychiatry 58:293–299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhosale UA, Yegnanarayan R, Agrawal A, Patil A (2019) Efficacy study of folic acid supplementation on homocysteine levels in adolescent epileptics taking antiepileptic drugs: a single blind randomized controlled clinical trial. Ann Neurosci 26:50–54

    Article  PubMed  Google Scholar 

  • Bottiglieri T, Arning E, Wasek B, Nunbhakdi-Craig V, Sontag JM, Sontag E (2012) Acute administration of L-DOPA induces changes in methylation metabolites, reduced protein phosphatase 2A methylation, and hyperphosphorylation of Tau protein in mouse brain. J Neurosci 32:9173–9181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brosnan JT, Jacobs RL, Stead LM, Brosnan ME (2004) Methylation demand: a key determinant of homocysteine metabolism. Acta Biochim Pol 51:405–413

    Article  CAS  PubMed  Google Scholar 

  • Demicheva E, Cui YF, Bardwell P, Barghorn S, Kron M, Meyer AH, Schmidt M, Gerlach B, Leddy M, Barlow E, O’Connor E, Choi CH, Huang L, Veldman GM, Rus H, Shabanzadeh AP, Tassew NG, Monnier PP, Muller T, Calabresi PA, Schoemaker H, Mueller BK (2015) Targeting repulsive guidance molecule A to promote regeneration and neuroprotection in multiple sclerosis. Cell Rep 10:1887–1898

    Article  CAS  PubMed  Google Scholar 

  • Dexter DT, Sian J, Rose S, Hindmarsh JG, Mann VM, Cooper JM, Wells FR, Daniel SE, Lees AJ, Schapira AH (1994) Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease. Ann Neurol 35:38–44

    Article  CAS  PubMed  Google Scholar 

  • Dorszewska J, Florczak J, Rozycka A, Kempisty B, Jaroszewska-Kolecka J, Chojnacka K, Trzeciak WH, Kozubski W (2007) Oxidative DNA damage and level of thiols as related to polymorphisms of MTHFR, MTR, MTHFD1 in Alzheimer’s and Parkinson’s diseases. Acta Neurobiol Exp (wars ) 67:113–129

    PubMed  Google Scholar 

  • El-Farahaty RM, El-Mitwalli A, Azzam H, Wasel Y, Elrakhawy MM, Hasaneen BM (2015) Atherosclerotic effects of long-term old and new antiepileptic drugs monotherapy: a cross-sectional comparative study. J Child Neurol 30:451–457

    Article  PubMed  Google Scholar 

  • Espay AJ, Okun MS (2023) Abandoning the Proteinopathy Paradigm in Parkinson Disease. JAMA Neurol 80:123–124

    Article  PubMed  Google Scholar 

  • Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K (2004) Levodopa and the progression of Parkinson’s disease. N Engl J Med 351:2498–2508

    Article  CAS  PubMed  Google Scholar 

  • Furukawa Y, Tomioka N, Sato W, Satoyoshi E, Hayashi K, Furukawa S (1989) Catecholamines increase nerve growth factor mRNA content in both mouse astroglial cells and fibroblast cells. FEBS Lett 247:463–467

    Article  CAS  PubMed  Google Scholar 

  • Galasko D, Simuni T (2022) Lack of Benefit of Iron Chelation in Early Parkinson’s Disease. N Engl J Med 387:2087–2088

    Article  PubMed  Google Scholar 

  • Guerra F, Girolimetti G, Beli R, Mitruccio M, Pacelli C, Ferretta A, Gasparre G, Cocco T, Bucci C (2019) Synergistic effect of mitochondrial and lysosomal dysfunction in Parkinson’s disease. Cells 8:452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hadtstein F, Vrolijk M (2021) Vitamin B-6-induced neuropathy: exploring the mechanisms of pyridoxine toxicity. Adv Nutr 12:1911–1929

    Article  PubMed  PubMed Central  Google Scholar 

  • Hawkins RA, Mokashi A, Simpson IA (2005) An active transport system in the blood-brain barrier may reduce levodopa availability. Exp Neurol 195:267–271

    Article  CAS  PubMed  Google Scholar 

  • Herrmann W, Knapp JP (2002) Hyperhomocysteinemia: a new risk factor for degenerative diseases. Clin Lab 48:471–481

    CAS  PubMed  Google Scholar 

  • Hinz M, Stein A, Cole T (2014) The Parkinson’s disease death rate: carbidopa and vitamin B6. Clin Pharmacol 6:161–169

    PubMed  PubMed Central  Google Scholar 

  • Isobe C, Murata T, Sato C, Terayama Y (2005) Increase of total homocysteine concentration in cerebrospinal fluid in patients with Alzheimer’s disease and Parkinson’s disease. Life Sci 77:1836–1843

    Article  CAS  PubMed  Google Scholar 

  • Isobe C, Abe T, Terayama Y (2010) L-Dopa therapy increases homocysteine concentration in cerebrospinal fluid from patients with Parkinson’s disease. J Clin Neurosci 17:717–721

    Article  CAS  PubMed  Google Scholar 

  • Jowaed A, Schmitt I, Kaut O, Wullner U (2010) Methylation regulates alpha-synuclein expression and is decreased in Parkinson’s disease patients’ brains. J Neurosci 30:6355–6359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalani K, Yan SF, Yan SS (2018) Mitochondrial permeability transition pore: a potential drug target for neurodegeneration. Drug Discov Today 23:1983–1989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamat PK, Kalani A, Kyles P, Tyagi SC, Tyagi N (2014) Autophagy of mitochondria: a promising therapeutic target for neurodegenerative disease. Cell Biochem Biophys 70:707–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kasai Y, Tachikawa M, Hirose S, Akanuma S, Hosoya K (2011) Transport systems of serine at the brain barriers and in brain parenchymal cells. J Neurochem 118:304–313

    Article  CAS  PubMed  Google Scholar 

  • Khot M, Sood A, Tryphena KP, Khan S, Srivastava S, Singh SB, Khatri DK (2022) NLRP3 inflammasomes: A potential target to improve mitochondrial biogenesis in Parkinson’s disease. Eur J Pharmacol 934:175300

    Article  CAS  PubMed  Google Scholar 

  • Klostermann F, Jugel C, Müller T, Marzinzik F (2012) Malnutritional neuropathy under intestinal levodopa infusion. J Neural Transm 119:369–372

    Article  CAS  PubMed  Google Scholar 

  • Korecka JA, Moloney EB, Eggers R, Hobo B, Scheffer S, Ras-Verloop N, Pasterkamp RJ, Swaab DF, Smit AB, van Kesteren RE, Bossers K, Verhaagen J (2017) Repulsive guidance molecule a (RGMa) induces neuropathological and behavioral changes that closely resemble Parkinson’s disease. J Neurosci 37:9361–9379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liedhegner EA, Steller KM, Mieyal JJ (2011) Levodopa activates apoptosis signaling kinase 1 (ASK1) and promotes apoptosis in a neuronal model: implications for the treatment of Parkinson’s disease. Chem Res Toxicol 24:1644–1652

    Article  PubMed  Google Scholar 

  • Malouf R, Grimley EJ (2003) The effect of vitamin B6 on cognition. Cochrane Database Syst Rev CD004393

  • Manca D, Cossu G, Murgia D, Molari A, Ferrigno P, Marcia E, Melis M (2009) Reversible encephalopathy and axonal neuropathy in Parkinson’s disease during duodopa therapy. Mov Disord 24:2293–2294

    Article  PubMed  Google Scholar 

  • Martignoni E, Tassorelli C, Nappi G, Zangaglia R, Pacchetti C, Blandini F (2007) Homocysteine and Parkinson’s disease: a dangerous liaison? J Neurol Sci 257:31–37

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP (2003) Methylation and acetylation in nervous system development and neurodegenerative disorders. Ageing Res Rev 2:329–342

    Article  CAS  PubMed  Google Scholar 

  • McCaddon A, Hudson P, Davies G, Hughes A, Williams JH, Wilkinson C (2001) Homocysteine and cognitive decline in healthy elderly. Dement Geriatr Cogn Disord 12:309–313

    Article  CAS  PubMed  Google Scholar 

  • Melamed E, Hefti F, Wurtman RJ (1980) Nonaminergic striatal neurons convert exogenous L-dopa to dopamine in parkinsonism. Ann Neurol 8:558–563

    Article  CAS  PubMed  Google Scholar 

  • Mothe AJ, Tassew NG, Shabanzadeh AP, Penheiro R, Vigouroux RJ, Huang L, Grinnell C, Cui YF, Fung E, Monnier PP, Mueller BK, Tator CH (2017) RGMa inhibition with human monoclonal antibodies promotes regeneration, plasticity and repair, and attenuates neuropathic pain after spinal cord injury. Sci Rep 7:10529

    Article  PubMed  PubMed Central  Google Scholar 

  • Miller JW (2002) Homocysteine, folate deficiency, and Parkinson’s disease. Nutr Rev 60:410–413

    Article  PubMed  Google Scholar 

  • Müller T (2008) Role of homocysteine in the treatment of Parkinson’s disease. Expert Rev Neurother 8:957–967

    Article  PubMed  Google Scholar 

  • Müller T (2022) What are the main considerations when prescribing pharmacotherapy for Parkinson’s disease? Expert Opin Pharmacother 23:745–750

    Article  PubMed  Google Scholar 

  • Müller T, Kuhn W (2006) Tolcapone decreases plasma levels of S-adenosyl-L-homocysteine and homocysteine in treated Parkinson’s disease patients. Eur J Clin Pharmacol 62:447–450

    Article  PubMed  Google Scholar 

  • Müller T, Kuhn W (2009) Cysteine elevation in levodopa-treated patients with Parkinson’s disease. Mov Disord 24:929–932

    Article  PubMed  Google Scholar 

  • Müller T, Kohlhepp W (2016) Hypomethylation in Parkinson’s disease: an epigenetic drug effect? Mov Disord 31:605

    Article  PubMed  Google Scholar 

  • Müller T, Kohlhepp W (2018) Nigral depigmentation reflects monoamine exhaustion as initial step to Parkinson’s disease. Med Hypotheses 110:46–49

    Article  PubMed  Google Scholar 

  • Müller T, Kuhn W (2023) Epigenetic drug effects in levodopa-treated patients with Parkinson’s disease. Mov Disord 38:710–711

    Article  PubMed  Google Scholar 

  • Müller T, Muhlack S (2009) Peripheral COMT inhibition prevents levodopa associated homocysteine increase. J Neural Transm (vienna ) 116:1253–1256

    Article  PubMed  Google Scholar 

  • Müller T, Muhlack S (2010) Acute homocysteine rise after repeated levodopa application in patients with Parkinson’s disease. Parkinsonism Relat Disord 16:688–689

    Article  PubMed  Google Scholar 

  • Müller T, Werne B, Fowler B, Kuhn W (1999) Nigral endothelial dysfunction, homocysteine, and Parkinson’s disease. Lancet 354:126–127

    Article  PubMed  Google Scholar 

  • Müller T, Renger K, Kuhn W (2004) Levodopa-associated increase of homocysteine levels and sural axonal neurodegeneration. Arch Neurol 61:657–660

    Article  PubMed  Google Scholar 

  • Müller T, Lang UE, Muhlack S, Welnic J, Hellweg R (2005) Impact of levodopa on reduced nerve growth factor levels in patients with Parkinson disease. Clin Neuropharmacol 28:238–240

    Article  PubMed  Google Scholar 

  • Müller T, Jugel C, Ehret R, Ebersbach G, Bengel G, Muhlack S, Klostermann F (2011a) Elevation of total homocysteine levels in patients with Parkinson’s disease treated with duodenal levodopa/carbidopa gel. J Neural Transm 118:1329–1333

    Article  PubMed  Google Scholar 

  • Müller T, Muhlack S (2011b) Cysteinyl-glycine reduction as marker for Levodopa induced oxidative stress in Parkinson’s disease patients. Mov Disord 26:543–546

    Article  PubMed  Google Scholar 

  • Müller T, Jugel C, Muhlack S, Klostermann F (2013a) Methyl group-donating vitamins elevate 3-O-methyldopa in patients with Parkinson disease. Clin Neuropharmacol 36:52–54

    Article  PubMed  Google Scholar 

  • Müller T, van LT, Cornblath DR, Odin P, Klostermann F, Grandas FJ, Ebersbach G, Urban PP, Valldeoriola F, Antonini A (2013b) Peripheral neuropathy in Parkinson's disease: levodopa exposure and implications for duodenal delivery. Parkinsonism Relat Disord 19: 501–507

  • Müller T, Barghorn S, Lütge S, Haas T, Mueller R, Gerlach B, Öhm G, Eilert K, Trommer I, Mueller BK (2015) Decreased levels of repulsive guidance molecule A in association with beneficial effects of repeated intrathecal triamcinolone acetonide application in progressive multiple sclerosis patients. J Neural Transm (vienna ) 122:841–848

    Article  PubMed  Google Scholar 

  • Müller T, Trommer I, Muhlack S, Mueller BK (2016) Levodopa increases oxidative stress and repulsive guidance molecule A levels: a pilot study in patients with Parkinson’s disease. J Neural Transm (vienna ) 123:401–406

    Article  PubMed  Google Scholar 

  • Müller T, Mueller BK, Riederer P (2021) Perspective: treatment for disease modification in chronic neurodegeneration. Cells 10:873

    Article  PubMed  PubMed Central  Google Scholar 

  • Müller T, Schlegel E, Zingler S, Thiede HM (2022) Effects of one-day application of Levodopa/Carbidopa/Entacapone versus Levodopa/Carbidopa/Opicapone in Parkinson’s disease patients. Cells 11:1511

    Article  PubMed  PubMed Central  Google Scholar 

  • Murer MG, Yan Q, Raisman-Vozari R (2001) Brain-derived neurotrophic factor in the control human brain, and in Alzheimer’s disease and Parkinson’s disease. Prog Neurobiol 63:71–124

    Article  CAS  PubMed  Google Scholar 

  • Nagatsu T, Nakashima A, Watanabe H, Ito S, Wakamatsu K, Zucca FA, Zecca L, Youdim M, Wulf M, Riederer P, Dijkstra JM (2023) The role of tyrosine hydroxylase as a key player in neuromelanin synthesis and the association of neuromelanin with Parkinson’s disease. J Neural Transm (vienna ) 130:611–625

    Article  CAS  PubMed  Google Scholar 

  • Nakaso K, Yasui K, Kowa H, Kusumi M, Ueda K, Yoshimoto Y, Takeshima T, Sasaki K, Nakashima K (2003) Hypertrophy of IMC of carotid artery in Parkinson’s disease is associated with L-DOPA, homocysteine, and MTHFR genotype. J Neurol Sci 207:19–23

    Article  CAS  PubMed  Google Scholar 

  • Naoi M, Dostert P, Yoshida M, Nagatsu T (1993) N-methylated tetrahydroisoquinolines as dopaminergic neurotoxins. Adv Neurol 60:212–217

    CAS  PubMed  Google Scholar 

  • Naoi M, Maruyama W, Niwa T, Nagatsu T (1994) Novel toxins and Parkinson’s disease: N-methylation and oxidation as metabolic bioactivation of neurotoxin. J Neural Transm Suppl 41:197–205

    CAS  PubMed  Google Scholar 

  • Naoi M, Maruyama W, Nakao N, Ibi T, Sahashi K, Benedetti MS (1998) (R)salsolinol N-methyltransferase activity increases in parkinsonian lymphocytes. Ann Neurol 43:212–216

    Article  CAS  PubMed  Google Scholar 

  • Ni G, Qin J, Li H, Chen Z, Zhou Y, Fang Z, Chen Y, Zhou J, Huang M, Zhou L (2015) Effects of antiepileptic drug monotherapy on one-carbon metabolism and DNA methylation in patients with epilepsy. PLoS ONE 10:e0125656

    Article  PubMed  PubMed Central  Google Scholar 

  • Nitta A, Furukawa Y, Hayashi K, Hiramatsu M, Kameyama T, Hasegawa T, Nabeshima T (1992) Denervation of dopaminergic neurons with 6-hydroxydopamine increases nerve growth factor content in rat brain. Neurosci Lett 144:152–156

    Article  CAS  PubMed  Google Scholar 

  • O’Suilleabhain PE, Sung V, Hernandez C, Lacritz L, Dewey RB, Bottiglieri T, az-Arrastia R (2004) Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations. Arch Neurol 61:865–868

    Article  PubMed  Google Scholar 

  • Oda W, Fujita Y, Baba K, Mochizuki H, Niwa H, Yamashita T (2021) Inhibition of repulsive guidance molecule-a protects dopaminergic neurons in a mouse model of Parkinson’s disease. Cell Death Dis 12:181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oestreicher E, Sengstock GJ, Riederer P, Olanow CW, Dunn AJ, Arendash GW (1994) Degeneration of nigrostriatal dopaminergic neurons increases iron within the substantia nigra: a histochemical and neurochemical study. Brain Res 660:8–18

    Article  CAS  PubMed  Google Scholar 

  • Ouilleabhain P, az-Arrastia R (2004) Levodopa elevates homocysteine: is this a problem? Arch Neurol 61:633–634

    Article  Google Scholar 

  • Pauls KAM, Toppila J, Koivu M, Eerola-Rautio J, Udd M, Pekkonen E (2021) Polyneuropathy monitoring in Parkinson’s disease patients treated with levodopa/carbidopa intestinal gel. Brain Behav 11:e2408

    Article  PubMed  PubMed Central  Google Scholar 

  • Picerno I, Chirico C, Condello S, Visalli G, Ferlazzo N, Gorgone G, Caccamo D, Ientile R (2007) Homocysteine induces DNA damage and alterations in proliferative capacity of T-lymphocytes: a model for immunosenescence? Biogerontology 8:111–119

    Article  CAS  PubMed  Google Scholar 

  • Postuma RB, Lang AE (2004) Homocysteine and levodopa: should Parkinson disease patients receive preventative therapy? Neurology 63:886–891

    Article  CAS  PubMed  Google Scholar 

  • Postuma RB, Espay AJ, Zadikoff C, Suchowersky O, Martin WR, Lafontaine AL, Ranawaya R, Camicioli R, Lang AE (2006) Vitamins and entacapone in levodopa-induced hyperhomocysteinemia: a randomized controlled study. Neurology 66:1941–1943

    Article  CAS  PubMed  Google Scholar 

  • Reitz C, Trenkwalder C, Kretzschmar K, Roesler A, v Eckardstein A, Berger K, (2006) Relation of cerebral small-vessel disease and brain atrophy to mild parkinsonism in the elderly. Mov Disord 21:1914–1919

    Article  PubMed  Google Scholar 

  • Riederer P, Berg D, Casadei N, Cheng F, Classen J, Dresel C, Jost W, Krüger R, Müller T, Reichmann H, Riess O, Storch A, Strobel S, Van ET, Volker HU, Winkler J, Winklhofer KF, Wullner U, Zunke F, Monoranu CM (2019) alpha-Synuclein in Parkinson’s disease: causal or bystander? J Neural Transm (Vienna) 126:815–840

    Article  PubMed  Google Scholar 

  • Riederer P, Monoranu C, Strobel S, Iordache T, Sian-Hulsmann J (2021) Iron as the concert master in the pathogenic orchestra playing in sporadic Parkinson’s disease. J Neural Transm (vienna ) 128:1577–1598

    Article  CAS  PubMed  Google Scholar 

  • Riederer P, Nagatsu T, Youdim MBH, Wulf M, Dijkstra JM, Sian-Huelsmann J (2023) Lewy bodies, iron, inflammation and neuromelanin: pathological aspects underlying Parkinson’s disease. J Neural Transm (vienna ) 130:627–646

    Article  CAS  PubMed  Google Scholar 

  • Sabens EA, Distler AM, Mieyal JJ (2010) Levodopa deactivates enzymes that regulate Thiol-Disulfide homeostasis and promotes neuronal cell death - implications for therapy of Parkinson’s disease. Biochemistry. https://doi.org/10.1021/bi9018658

    Article  PubMed  Google Scholar 

  • Sachdev PS (2005) Homocysteine and brain atrophy. Prog Neuropsychopharmacol Biol Psychiatry 29:1152–1161

    Article  CAS  PubMed  Google Scholar 

  • Schwartz RS, Halliday GM, Cordato DJ, Kril JJ (2012) Small-vessel disease in patients with Parkinson’s disease: a clinicopathological study. Mov Disord 27:1506–1512

    Article  PubMed  Google Scholar 

  • Schwartz RS, Halliday GM, Soh D, Cordato DJ, Kril JJ (2018) Impact of small vessel disease on severity of motor and cognitive impairment in Parkinson’s disease. J Clin Neurosci 58:70–74

    Article  PubMed  Google Scholar 

  • Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, Jenner P, Marsden CD (1994a) Alterations in glutathione levels in Parkinson’s disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 36:348–355

    Article  CAS  PubMed  Google Scholar 

  • Sian J, Dexter DT, Lees AJ, Daniel S, Jenner P, Marsden CD (1994b) Glutathione-related enzymes in brain in Parkinson’s disease. Ann Neurol 36:356–361

    Article  CAS  PubMed  Google Scholar 

  • Sian-Hülsmann J, Riederer P (2021) The Nigral Coup in Parkinson's disease by alpha-Synuclein and its associated rebels. Cells 10

  • Spence JD, Hankey GJ (2022) Problem in the recent american heart association guideline on secondary stroke prevention: B Vitamins to lower homocysteine do prevent stroke. Stroke 53:2702–2708

    Article  PubMed  Google Scholar 

  • Spence JD, Yi Q, Hankey GJ (2017) B vitamins in stroke prevention: time to reconsider. Lancet Neurol 16:750–760

    Article  CAS  PubMed  Google Scholar 

  • Tanner CM, Ross GW, Jewell SA, Hauser RA, Jankovic J, Factor SA, Bressman S, Deligtisch A, Marras C, Lyons KE, Bhudhikanok GS, Roucoux DF, Meng C, Abbott RD, Langston JW (2009) Occupation and risk of parkinsonism: a multicenter case-control study. Arch Neurol 66:1106–1113

    Article  PubMed  Google Scholar 

  • Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, Marras C, Bhudhikanok GS, Kasten M, Chade AR, Comyns K, Richards MB, Meng C, Priestley B, Fernandez HH, Cambi F, Umbach DM, Blair A, Sandler DP, Langston JW (2011) Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect 119:866–872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tawfik A, Samra YA, Elsherbiny NM, Al-Shabrawey M (2020) Implication of Hyperhomocysteinemia in Blood Retinal Barrier (BRB) dysfunction. Biomolecules 10:119. https://doi.org/10.3390/biom10081119

    Article  CAS  Google Scholar 

  • Toth C, Breithaupt K, Ge S, Duan Y, Terris JM, Thiessen A, Wiebe S, Zochodne DW, Suchowersky O (2010) Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson disease. Ann Neurol 68:28–36

    Article  CAS  PubMed  Google Scholar 

  • Tryphena KP, Anuradha U, Kumar R, Rajan S, Srivastava S, Singh SB, Khatri DK (2022) Understanding the involvement of microRNAs in mitochondrial dysfunction and their role as potential biomarkers and therapeutic targets in Parkinson’s disease. J Alzheimers Dis. https://doi.org/10.3233/JAD-220449

    Article  PubMed  Google Scholar 

  • Valkovic P, Benetin J, Blazicek P, Valkovicova L, Gmitterova K, Kukumberg P (2005) Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients. Parkinsonism Relat Disord 11:253–256

    Article  PubMed  Google Scholar 

  • Whone AL, Watts RL, Stoessl AJ, Davis M, Reske S, Nahmias C, Lang AE, Rascol O, Ribeiro MJ, Remy P, Poewe WH, Hauser RA, Brooks DJ (2003) Slower progression of Parkinson’s disease with ropinirole versus levodopa: The REAL-PET study. Ann Neurol 54:93–101

    Article  CAS  PubMed  Google Scholar 

  • Wise RM, Wagener A, Fietzek UM, Klopstock T, Mosharov EV, Zucca FA, Sulzer D, Zecca L, Burbulla LF (2022) Interactions of dopamine, iron, and alpha-synuclein linked to dopaminergic neuron vulnerability in Parkinson’s disease and Neurodegeneration with Brain Iron Accumulation disorders. Neurobiol Dis 175:105920

    Article  CAS  PubMed  Google Scholar 

  • Wong A, Mok V, Fan YH, Lam WW, Liang KS, Wong KS (2006) Hyperhomocysteinemia is associated with volumetric white matter change in patients with small vessel disease. J Neurol 253:441–447

    Article  PubMed  Google Scholar 

  • Wüllner U, Kaut O, deBoni L, Piston D, Schmitt I (2016) DNA methylation in Parkinson’s disease. J Neurochem 139(Suppl 1):108–120

    Article  PubMed  Google Scholar 

  • Zhao WQ, Williams Z, Shepherd KR, Reuben JS, Lee ES, Rling-Reed S, Lamango N, Soliman KF, Charlton CG (2002) S-adenosyl-methionine-induced apoptosis in PC12 cells. J Neurosci Res 69:519–529

    Article  CAS  PubMed  Google Scholar 

  • Zoccolella S, Martino D, Defazio G, Lamberti P, Livrea P (2006) Hyperhomocysteinemia in movement disorders: Current evidence and hypotheses. Curr Vasc Pharmacol 4:237–243

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088, Berlin, Germany

    Thomas Müller

  2. Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Margarete-Höppel Platz 1, 97080, Würzburg, Germany

    Peter Riederer

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Müller, T., Riederer, P. The vicious circle between homocysteine, methyl group-donating vitamins and chronic levodopa intake in Parkinson’s disease. J Neural Transm (2023). https://doi.org/10.1007/s00702-023-02666-x

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