The deposition of the abundant presynaptic brain protein alpha-synuclein as 
fibrillary aggregates in neurons or glial cells is a hallmark lesion in a subset 
of neurodegenerative disorders. These disorders include Parkinson's disease 
(PD), dementia with Lewy bodies (DLB) and multiple system atrophy, collectively 
referred to as synucleinopathies. Importantly, the identification of missense 
mutations in the alpha-synuclein gene in some pedigrees of familial PD has 
strongly implicated alpha-synuclein in the pathogenesis of PD and other 
synucleinopathies. However, specific post-translational modifications that 
underlie the aggregation of alpha-synuclein in affected brains have not, as yet, 
been identified. Here, we show by mass spectrometry analysis and studies with an 
antibody that specifically recognizes phospho-Ser 129 of alpha-synuclein, that 
this residue is selectively and extensively phosphorylated in synucleinopathy 
lesions. Furthermore, phosphorylation of alpha-synuclein at Ser 129 promoted 
fibril formation in vitro. These results highlight the importance of 
phosphorylation of filamentous proteins in the pathogenesis of neurodegenerative 
disorders.