Zusammenfassung
Nach wie vor sind die Ursachen für die Entstehung eines idiopathischen Parkinson-Syndroms weitgehend unbekannt und Gegenstand intensiver Forschungsaktivitäten. Hinsichtlich der Erforschung der Pathogenese wurden in den letzten Jahren bedeutsame Fortschritte erzielt. So lieferten auch die seltenen hereditären Erkrankungen wertvolle Hinweise für die möglichen Pathogenesemechanismen bei den idiopathischen Fällen. In diesem kurzen Übersichtsartikel wird ein Überblick über die PARK-Gene gegeben und die ihnen bei Mutationen mutmaßlich zugrunde liegenden toxischen Auswirkungen eingegangen, soweit sie bekannt sind. Darüber hinaus werden weitere, für die Pathogenese bedeutsame Faktoren wie Umweltfaktoren, Entzündungsvorgänge, Proteasom, mitochondriale Dysfunktion, Eisentoxizität und Neuromelanin, Dopamin, Glutamat und Exzitotoxizität angesprochen. Außerdem wird auf die kontroverse Diskussion zum Absterbmechanismus der dopaminergen Neuronen (Apoptose versus Nekrose) eingegangen und schließlich der oxidative Stress als ein allen pathogenetischen Faktoren gemeinsames Bindeglied präsentiert.
Abstract
Intensive research activities are carried out to elucidate the causes underlying idiopathic Parkinson's disease. In recent years, significant progress has been achieved concerning the pathogenetic mechanisms and the hereditary cases have contributed valuable insights. This short review outlines the putative toxic mechanisms connected with mutations of the PARK genes, and summarizes other potentially important factors like environmental causes, inflammation, proteasome, mitochondrial dysfunction, iron toxicity and neuromelanin, dopamine, glutamate and excitotoxicity. The controversial discussion about the mechanism of dopaminergic cell death (apoptosis vs. necrosis) will be followed, and finally, oxidative stress will be presented as an intersecting common pathway of all pathogenetic factors.
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Gabriele GillePhD
Technische Universität Dresden · Abteilung für Neurologie
Fetscherstraße 74
01307 Dresden
Email: Gabriele.Gille@neuro.med.tu-dresden.de
