パーキンソン病・ジストニアの関連遺伝子

Causative Gene and its Associated Gene for Parkinson Disease and Dystonia

はじめに

　パーキンソン病（Parkinson disease：PD），ジストニア（dystonia）は不随意運動を来す病態の基礎疾患として頻度の高い疾患である。それぞれ遺伝性，孤発性の群があり，遺伝性の群については病因遺伝子の同定がなされている。また，孤発性パーキンソン病については疾患関連遺伝子についての報告が数多くなされている。ここではそれぞれについて，臨床像，遺伝子について概説する。遺伝子に関する情報は日々更新されており，ここでは2008年12月現在の状況を記す。

Abstract

　Parkinson disease (PD) and dystonia are two major part of neurodegenerative disorders.　The underlying cause of PD development has been considered to be a combination of genetic factors and environmental substrates.　In case of dystonia,which includes primary sporadic dystonia,such as task specific dystonia,cervical dystonia and so on,are also considered to associate with unknown vulnerable genetic factors.　In this paper,the clinical features and causative genes for PD and dystonia were described; especially in particular,the description of those genes associated with the PARK and DYT series were provided.　Most of the identified causative genes for PD are associated with the protein degradation and cell death process via convergent mechanisms such as ubiquitin-proteasome system,mitochondrial dysfunction,oxidative stress,and lysosomal system (autophagia).　On the other hand,the pathogenic mechanism for dystonia is gradually discovered to be divergent suggested by identified genes,such as torsinA,GCH1,etc,which is compatible and well understood with the divergent expression of dystonia phenotype.　Another breakthroughs are required to investigate the treatment of both PD and dystonia based on the pathogenic mechanisms.