α-Synuclein aggregation and neurodegenerative diseases

α-Synuclein is a neuronal protein originally identified in Alzheimer's disease (AD) amyloid plaques in 1993 and named non-Aβ 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 α-synuclein gene in certain autosomal-dominant early onset familial Parkinson's disease (PD) has greatly promoted the understanding of the role of α-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 α-synuclein may play a central role in several neurodegenerative disorders because of the presence of insoluble α-synuclein as the major fibrillar component of inclusion bodies. From the cloning of the human α-synuclein cDNA in 1993 to the present, α-synuclein has been carefully documented in many aspects. In this article, we review the progress of studies on α-synuclein and its role in α-synuclein-related neurodegenerative diseases. 1. The structure of the α-synuclein gene and

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