Mechanisms of neuronal death in synucleinopathy.
alpha-synuclein is a key molecule in the pathogenesis of synucleinopathy including Parkinson's disease and multiple system atrophy. In this mini-review, we mainly focus on recent data obtained from cellular models of synucleinopathy and discuss the possible mechanisms of neurodegeneration. Recent progress suggests that the aggregate formation of alpha-synuclein is cytoprotective and that its precursor oligomer (protofibril) may be cytotoxic. The catechol-derived quinones are the candidate molecules that facilitate the oligomer formation of alpha-synuclein. Furthermore, the cellular membranes are shown to be the primary targets injured by mutant alpha-synucleins, and the mitochondrial dysfunction seems to be an initial step in the neuronal death.
Takeda
Atsushi
A
Department of Neurology, Center for Asian Traditional Medicine Research, Graduate School of Medicine, Tohoku University, Aobaku, Sendai 980-8574, Japan.
Hasegawa
Takafumi
T
Matsuzaki-Kobayashi
Michiko
M
Sugeno
Naoto
N
Kikuchi
Akio
A
Itoyama
Yasuto
Y
Furukawa
Katsutoshi
K