Involvement of α-synuclein in Parkinson's disease and other neurodegenerative disorders

A major step in the elucidation of the pathogenesis of neurodegenerative disorders was the identification of a mutation in the α-synuclein gene in autosomal dominant Parkinson's disease (PD). α-Synuclein is the main component of Lewy bodies (LB), the neuropathological hallmark of PD. Moreover, a fragment of a-synuclein (NAC) is the second major component of amyloid plaques in Alzheimer's disease (AD). Recent studies of other neurodegenerative disorders such as dementia with LB (DLB), multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS) also revealed intracellular accumulations of α-synuclein in affected brain regions. This may indicate that these disorders partially share common pathogenic mechanisms. Recent data provide first insights into the physiological function of α-synuclein and support the concept of an essential role of α-synuclein in neurodegeneration. Increasing knowledge on the pathogenic molecular mechanisms of neurodegeneration and of the pathophysiological function of α-synuclein in particular may influence future development of therapeutic strategies in neurodegenerative disorders.