Psychosomatik und Konsiliarpsychiatrie

, Volume 2, Issue 1, pp 44–49

Einfluss von Alkohol auf Homocystein-Metabolismus und Epigenetik

Neue medizinische Methoden
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Zusammenfassung

Alkoholabhängigkeit und die damit verbundenen Folgeerkrankungen spielen in unserer Gesellschaft eine wichtige Rolle. Prävention und bessere Therapien erfordern ein umfassendes Verständnis der Pathomechanismen alkoholbedingter Erkrankungen. Viele dieser Störungen lassen sich erst mit Hilfe der molekularbiologischer Vorgänge erklären. Die Epigenetik ist in diesem Zusammenhang von besonderer Bedeutung.

Chronischer Alkoholkonsum ist mit erhöhten Homocystein-Plasmaspiegeln assoziiert. Das Aminosäurederivat Homocystein wirkt als Agonist am NMDA-Rezeptor. Die durch eine Hyperhomocysteinämie induzierte Exzitotoxizität bietet einen Erklärungsansatz für epiletische Anfälle im Alkoholentzug und die alkoholbedingte Hirnvolumenreduktion. Weiterhin wirken sich erhöhte Spiegel auf epigenetische Regulationsmechanismen aus. Es werden Dysregulationen der DNA-Methylierung beobachtet. Betroffen ist dabei sowohl die globale DNA-Methylierung als auch der Methylierungsstatus der CpG-Inseln auf Ebene der Genpromotoren. Untersuchungen der bei Suchterkrankungen wichtigen Gene, HERP und Alpha Synuclein, zeigen eine Homocystein-assoziierte globale DNA-Hypermethylierung und eine Hypermethylierung ihres Promoters. Diese Befunde erklären erstmals einen neuen molekulargenetischen Mechanismus, der eine Teilerklärung für die durch Homocystein bedingten Störungen bei Alkoholabhängigkeit darstellt.

Schlüsselwörter

Alkohol Alkoholentzug DNA-Methylierung Epigenetik Homocystein 

The influence of alcohol on homocysteine metabolism and epigenetics

Abstract

Alcohol dependence and alcohol-associated diseases play an important role in nowadays society. Providing adequate therapy and prevention demands a broad understanding of moleculare mechanisms of alcohol-associated diseases. In this context „Epigenetic“ plays a significant role. Chronic alcohol-consumption in patients with alcohol dependence is associated with elevated homocysteine levels. The amino acid homocysteine acts as an agonist at the NMDA-receptor.

Excitotoxcity, induced by hyperhomocysteineaemia, offers an explanation for alcohol-withdrawal seizures and alcoholism-associated brain atrophy. Furthermore elevated levels effect epigenetic regulation-mechanisms. Global DNA-methylation is affected as well as promoterspecific methylation-status. Recent studies of genes (i.e. HERP, Alpha-Synnuclein), involved in addictive disorders, showed a global DNA-hypermethylation and a hypermethylation of their promoters. These findings offer a first moleculargenetic explanation for homocysteine-induced dysfunctions in patients with alcohol dependence.

Keywords

alcohol alcoholwithdrawal DNA-methylation epigenetics homocysteine 

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Copyright information

© Steinkopff-Verlag 2008

Authors and Affiliations

  1. 1.Psychiatrische und Psychotherapeutische KlinikFriedrich-Alexander-Universität zu Erlangen-Nürnberg ErlangenDeutschland

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