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Progress in the pathogenesis and genetics of Parkinson's disease

2008; Royal Society; Volume: 363; Issue: 1500 Linguagem: Inglês

10.1098/rstb.2008.2273

1471-2970

Yoshikuni Mizuno, Nobutaka Hattori, Shinichiro Kubo, Shigeto Sato, Kenya Nishioka, Taku Hatano, Hiroyuki Tomiyama, Manabu Funayama, Yutaka Machida, Hideki Mochizuki,

Neurological disorders and treatments

Recent progresses in the pathogenesis of sporadic Parkinson's disease (PD) and genetics of familial PD are reviewed. There are common molecular events between sporadic and familial PD, particularly between sporadic PD and PARK1 -linked PD due to α - synuclein ( SNCA ) mutations. In sporadic form, interaction of genetic predisposition and environmental factors is probably a primary event inducing mitochondrial dysfunction and oxidative damage resulting in oligomer and aggregate formations of α-synuclein. In PARK1 -linked PD, mutant α-synuclein proteins initiate the disease process as they have increased tendency for self-aggregation. As highly phosphorylated aggregated proteins are deposited in nigral neurons in PD, dysfunctions of proteolytic systems, i.e. the ubiquitin–proteasome system and autophagy–lysosomal pathway, seem to be contributing to the final neurodegenerative process. Studies on the molecular mechanisms of nigral neuronal death in familial forms of PD will contribute further on the understanding of the pathogenesis of sporadic PD.