Alpha-synuclein aggregation and neurodegenerative diseases.
Alpha-synuclein is a neuronal protein originally identified in Alzheimer's disease (AD) amyloid plaques in 1993 and named non-Abeta component precursor (NACP) [92]. Later, the discovery of two missense mutations (G88C and G209A), which resulted in Ala30Pro (A30P) and Ala53Thr (A53T) substitutions, of the alpha-synuclein gene in certain autosomal-dominant early onset familial Parkinson's disease (PD) has greatly promoted the understanding of the role of alpha-synuclein in the pathogenesis of neurodegenerative diseases, such as PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) [5,6,51,75]. At present, it is widely accepted that alpha-synuclein may play a central role in several neurodegenerative disorders because of the presence of insoluble alpha-synuclein as the major fibrillar component of inclusion bodies. From the cloning of the human alpha-synuclein cDNA in 1993 to the present, alpha-synuclein has been carefully documented in many aspects. In this article, we review the progress of studies on alpha-synuclein and its role in alpha-synuclein-related neurodegenerative diseases.
Department of Neural Plasticity, Tokyo Institute of Psychiatry, Tokyo 156-8585, Japan.
Qiu-Lan
QL
Ma
Piu
P
Chan
Mitsunobu
M
Yoshii
Kenji
K
Uéda
D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004195:Disease Models, Animal; D004330:Drosophila; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D010750:Phosphoproteins; D051843:Synucleins; D051844:alpha-Synuclein
D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein