[Analysis of alpha-synuclein and its significance].
Filamentous alpha-synuclein deposition is the defining hallmark of neurodegenerative synucleinopathies. The onset and progression of these diseases are thought to be related the formation of the alpha-synuclein filaments. We have analyzed posttranslational modifications of the filamentous alpha-synuclein in synucleinopathy brains by biochemical and protein chemical techniques. Mass spectrometric analysis revealed that deposited alpha-synuclein is highly phosphorylated at Ser129. We also found that alpha-synuclein is ubiquitinated in several synucleinopathy brains. The ubiquitination sites of soluble and filamentous alpha-synuclein were determined. These data have important implications for understanding the formation of alpha-synuclein filaments in synucleinopathy brains.
Nonaka
Takashi
T
Department of Molecular Neurobiology, Tokyo Institute of Psychiatry.
Iwatsubo
Takeshi
T
Hasegawa
Masato
M
D001923:Brain Chemistry; D006801:Humans; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D020734:Parkinsonian Disorders; D010766:Phosphorylation; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein