Koffein, Schokolade und Adenosin A2A Rezeptorantagonisten in der Behandlung des Parkinson Syndroms

Zusammenfassung

Hintergrund Patienten mit einem idiopathischen Parkinson-Syndrom können offenbar vom Koffeinkonsum profitieren, wie bereits eine Reihe experimenteller und klinischer Studien belegen.

Methodik Die Übersichtsarbeit untersuchte die vorliegende Literatur zu Koffein und Parkinson.

Ergebnisse Koffein kann die Blut-Hirn-Schranke durchdringen und übt seine biologischen Effekte überwiegend durch Antagonisierung von Adenosin-Rezeptoren aus. Zahlreiche Studien weisen darauf hin, dass Koffein und seine Derivate Theobromin und Theophylin mit einem reduzierten Parkinsonrisiko verbunden sind. Koffein und Adenosin-Antagonisten verringern die Exzitotoxizität durch Glutamat. Evidenz aus Tiermodellen untermauert das Potential des A_2A Rezeptorantagonismus als innovative Krankheits-verändernde Zielstruktur bei Parkinson

Schlussfolgerung Die vorliegenden Ergebnisse zeigen, dass die Untersuchung und Synthese von Xanthin-Derivaten sowie deren Analyse in klinischen Studien ein vielversprechender Ansatz in der Therapie neurodegenerativer Erkrankungen sein könnten.

Abstract

Background Patients with Parkinson’s disease can apparently benefit from caffeine consumption, as a number of experimental and clinical studies have already shown.

Methods The review examined the available literature on caffeine and Parkinson’s disease.

Results Caffeine can penetrate the blood-brain barrier and exerts its biological effects mainly by antagonizing adenosine receptors. Numerous studies indicate that caffeine and its derivatives theobromine and theophylline are associated with a reduced risk of Parkinson’s disease. Caffeine and adenosine antagonists reduce the excitotoxicity caused by glutamate. Evidence from animal models supports the potential of A2A receptor antagonism as an innovative disease-modifying target in Parkinson’s disease

Conclusion The present review shows that the investigation and synthesis of xanthine derivatives as well as their analysis in clinical studies could be a promising approach in the therapy of neurodegenerative diseases.

Schlüsselwörter

Koffein - Schokolade - idiopathisches Parkinson Syndrom - Neuroprotektion

Key Words

Caffeine - chocolade - Parkinson’s disease - neuroprotection

Publication History

Received: 25 October 2021

Accepted: 06 February 2022

Article published online:
18 May 2022

• Literatur

• 1 Heinzel S, Berg D, Binder S. et al. Do We Need to Rethink the Epidemiology and Healthcare Utilization of Parkinson’s Disease in Germany?. Front Neurol 2018; 9: 500
• 2 Solinas M, Ferre S, You ZB. et al. Caffeine induces dopamine and glutamate release in the shell of the nucleus accumbens. J Neurosci 2002; 22: 6321-6324
• 3 Olopade F, Femi-Akinlosotu O, Adekanmbi A. et al. Chronic Caffeine Ingestion Improves Motor Function and Increases Dendritic Length and Arborization in the Motor Cortex, Striatum, and Cerebellum. Journal of Caffeine and Adenosine Research 2021; 11: 3-14
• 4 Sheth S, Brito R, Mukherjea D. et al. Adenosine receptors: expression, function and regulation. Int J Mol Sci 2014; 15: 2024-2052
• 5 Fredholm BB, Svenningsson P. Why target brain adenosine receptors? A historical perspective. Parkinsonism Relat Disord 2020; 80: S3-s6
• 6 Camandola S, Plick N, Mattson MP. Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease. Neurochem Res 2019; 44: 214-227
• 7 Chen JF, Schwarzschild MA. Do caffeine and more selective adenosine A2A receptor antagonists protect against dopaminergic neurodegeneration in Parkinson’s disease?. Parkinsonism Relat Disord 2020; 80: S45-S53
• 8 Schepici G, Silvestro S, Bramanti P. et al. Caffeine: An Overview of Its Beneficial Effects in Experimental Models and Clinical Trials of Parkinson’s Disease. Int J Mol Sci 2020; 21
• 9 Ribeiro JA, Sebastião AM. Caffeine and adenosine. J Alzheimers Dis 2010; 20: S3-S15
• 10 Forth W, Adam O. Coffein: Umgang mit einem Genussmittel, das auch pharmakologische Wirkungen entfalten kann. Dtsch Arztebl International 2001; 98: 2816
• 11 Wolz M, Schleiffer C, Klingelhofer L. et al. Comparison of chocolate to cacao-free white chocolate in Parkinson’s disease: a single-dose, investigator-blinded, placebo-controlled, crossover trial. J Neurol 2012; 259: 2447-2451
• 12 Wolz M, Kaminsky A, Lohle M. et al. Chocolate consumption is increased in Parkinson’s disease. Results from a self-questionnaire study. J Neurol 2009; 256: 488-492
• 13 Moreira A, Diogenes MJ, de Mendonca A. et al. Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline. J Alzheimers Dis 2016; 53: 85-93
• 14 Janitschke D, Lauer AA, Bachmann CM. et al. Methylxanthines and Neurodegenerative Diseases: An Update. Nutrients 2021; 13
• 15 Ross GW, Abbott RD, Petrovitch H. et al. Association of Coffee and Caffeine Intake With the Risk of Parkinson Disease. JAMA. 2000; 283: 2674-2679
• 16 Sääksjärvi K, Knekt P, Rissanen H. et al. Prospective study of coffee consumption and risk of Parkinson’s disease. Eur J Clin Nutr 2008; 62: 908-915
• 17 Kyrozis A, Ghika A, Stathopoulos P. et al. Dietary and lifestyle variables in relation to incidence of Parkinson’s disease in Greece. Eur J Epidemiol 2013; 28: 67-77
• 18 Powers KM, Kay DM, Factor SA. et al. Combined effects of smoking, coffee, and NSAIDs on Parkinson’s disease risk. Mov Disord 2008; 23: 88-95
• 19 Hu G, Bidel S, Jousilahti P. et al. Coffee and tea consumption and the risk of Parkinson’s disease. Mov Disord 2007; 22: 2242-2248
• 20 Ascherio A, Chen H, Schwarzschild MA. et al. Caffeine, postmenopausal estrogen, and risk of Parkinson’s disease. Neurology 2003; 60: 790-795
• 21 Ascherio A, Weisskopf MG, O’Reilly EJ. et al. Coffee consumption, gender, and Parkinson’s disease mortality in the cancer prevention study II cohort: the modifying effects of estrogen. Am J Epidemiol 2004; 160: 977-984
• 22 Wirdefeldt K, Gatz M, Pawitan Y. et al. Risk and protective factors for Parkinson’s disease: a study in Swedish twins. Ann Neurol 2005; 57: 27-33
• 23 Liu R, Guo X, Park Y. et al. Caffeine intake, smoking, and risk of Parkinson disease in men and women. Am J Epidemiol 2012; 175: 1200-1207
• 24 Paganini-Hill A. Risk factors for parkinson’s disease: the leisure world cohort study. Neuroepidemiology 2001; 20: 118-124
• 25 Tan LC, Koh WP, Yuan JM. et al. Differential effects of black versus green tea on risk of Parkinson’s disease in the Singapore Chinese Health Study. Am J Epidemiol 2008; 167: 553-560
• 26 Ascherio A, Zhang SM, Hernán MA. et al. Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women. Ann Neurol 2001; 50: 56-63
• 27 Xu K, Xu YH, Chen JF. et al. Neuroprotection by caffeine: time course and role of its metabolites in the MPTP model of Parkinson’s disease. Neuroscience 2010; 167: 475-481
• 28 Palacios N, Gao X, McCullough ML. et al. Caffeine and risk of Parkinson’s disease in a large cohort of men and women. Mov Disord 2012; 27: 1276-1282
• 29 Xu K, Di Luca DG, Orru M. et al. Neuroprotection by caffeine in the MPTP model of parkinson’s disease and its dependence on adenosine A2A receptors. Neuroscience 2016; 322: 129-137
• 30 Qi H, Li S. Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson’s disease. Geriatr Gerontol Int 2014; 14: 430-439
• 31 Hong CT, Chan L, Bai CH. The Effect of Caffeine on the Risk and Progression of Parkinson’s Disease: A Meta-Analysis. Nutrients 2020; 12
• 32 Bakshi R, Macklin EA, Hung AY. et al. Associations of Lower Caffeine Intake and Plasma Urate Levels with Idiopathic Parkinson’s Disease in the Harvard Biomarkers Study. J Parkinsons Dis 2020; 10: 505-510
• 33 Altman RD, Lang AE, Postuma RB. Caffeine in Parkinson’s disease: a pilot open-label, dose-escalation study. Mov Disord 2011; 26: 2427-2431
• 34 Simon DK, Wu C, Tilley BC. et al. Caffeine and Progression of Parkinson Disease: A Deleterious Interaction With Creatine. Clin Neuropharmacol 2015; 38: 163-169
• 35 Postuma RB, Anang J, Pelletier A. et al. Caffeine as symptomatic treatment for Parkinson disease (Café-PD): A randomized trial. Neurology 2017; 89: 1795-1803
• 36 Fujimaki M, Saiki S, Li Y. et al. Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease. Neurology 2018; 90: e404-e411
• 37 Crotty GF, Maciuca R, Macklin EA. et al. Association of caffeine and related analytes with resistance to Parkinson disease among LRRK2 mutation carriers: A metabolomic study. Neurology. 2020; 95: e3428-e3437
• 38 Ohmichi T, Kasai T, Kosaka T. et al. Biomarker repurposing: Therapeutic drug monitoring of serum theophylline offers a potential diagnostic biomarker of Parkinson’s disease. PLoS One 2018; 13: e0201260
• 39 Teo KC, Ho SL. Monoamine oxidase-B (MAO-B) inhibitors: implications for disease-modification in Parkinson’s disease. Transl Neurodegener 2013; 2: 19
• 40 Chen JF, Xu K, Petzer JP. et al. Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson’s disease. J Neurosci 2001; 21: Rc143
• 41 Aguiar LMV, Nobre HV, Macêdo DS. et al. Neuroprotective effects of caffeine in the model of 6-hydroxydopamine lesion in rats. Pharmacology Biochemistry and Behavior 2006; 84: 415-419
• 42 Zhou ZD, Xie SP, Saw WT. et al. The Therapeutic Implications of Tea Polyphenols Against Dopamine (DA) Neuron Degeneration in Parkinson’s Disease (PD). Cells. 2019; 8
• 43 Clark J, Simon DK. Transcribe to survive: transcriptional control of antioxidant defense programs for neuroprotection in Parkinson’s disease. Antioxid Redox Signal 2009; 11: 509-528
• 44 Rozan P, Hidalgo S, Nejdi A. et al. Preventive antioxidant effects of cocoa polyphenolic extract on free radical production and cognitive performances after heat exposure in Wistar rats. J Food Sci 2007; 72: S203-S206
• 45 Sonsalla PK, Wong LY, Harris SL. et al. Delayed caffeine treatment prevents nigral dopamine neuron loss in a progressive rat model of Parkinson’s disease. Exp Neurol 2012; 234: 482-487
• 46 Costa MS, Botton PH, Mioranzza S. et al. Caffeine prevents age-associated recognition memory decline and changes brain-derived neurotrophic factor and tirosine kinase receptor (TrkB) content in mice. Neuroscience 2008; 153: 1071-1078
• 47 Xu K, Di Luca DG, Orrú M. et al. Neuroprotection by caffeine in the MPTP model of parkinson’s disease and its dependence on adenosine A2A receptors. Neuroscience 2016; 322: 129-137
• 48 Khadrawy YA, Salem AM, El-Shamy KA. et al. Neuroprotective and Therapeutic Effect of Caffeine on the Rat Model of Parkinson’s Disease Induced by Rotenone. Journal of Dietary Supplements 2017; 14: 553-572
• 49 Luan Y, Ren X, Zheng W. et al. Chronic Caffeine Treatment Protects Against alpha-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum. Front Neurosci 2018; 12: 301
• 50 Rohilla S, Bansal R, Kachler S. et al. Synthesis, biological evaluation and molecular modelling studies of 1,3,7,8-tetrasubstituted xanthines as potent and selective A(2A) AR ligands with in vivo efficacy against animal model of Parkinson’s disease. Bioorg Chem 2019; 87: 601-612
• 51 Pardo M, Paul NE, Collins-Praino LE. et al. The non-selective adenosine antagonist theophylline reverses the effects of dopamine antagonism on tremor, motor activity and effort-based decision-making. Pharmacol Biochem Behav 2020; 198: 173035
• 52 Socala K, Szopa A, Serefko A. et al. Neuroprotective Effects of Coffee Bioactive Compounds: A Review. Int J Mol Sci 2020; 22
• 53 Dall’Igna OP, Porciúncula LO, Souza DO. et al. Neuroprotection by caffeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity. Br J Pharmacol 2003; 138: 1207-1209
• 54 Kelsey JE, Langelier NA, Oriel BS. et al. The effects of systemic, intrastriatal, and intrapallidal injections of caffeine and systemic injections of A2A and A1 antagonists on forepaw stepping in the unilateral 6-OHDA-lesioned rat. Psychopharmacology (Berl) 2009; 201: 529-539
• 55 Ren X, Chen JF. Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms. Front Neurosci 2020; 14: 602697
• 56 Jenner P, Mori A, Aradi SD. et al. Istradefylline – a first generation adenosine A(2A) antagonist for the treatment of Parkinson’s disease. Expert Rev Neurother 2021; 21: 317-333