Synthetic filaments assembled from C-terminally truncated alpha-synuclein.
Recently two point mutations in the alpha-synuclein gene have been found in familial Parkinson's disease. The characteristic fibrous neuropathological lesions of Parkinson's and other neurodegenerative diseases have been shown to stain strongly with antibodies against alpha-synuclein and extracted filaments have been labelled with anti-alpha-synuclein antibodies. In view of the close involvement of alpha-synuclein filaments with pathology, it was important to establish an in vitro assembly system. We report here that C-terminally truncated recombinant alpha-synuclein readily assembles into filaments resembling those isolated from diseased brain and suggest that truncation by proteolysis may play a role in the pathological process.
Crowther
R A
RA
Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK.
Jakes
R
R
Spillantini
M G
MG
Goedert
M
M
D000409:Alanine; D019943:Amino Acid Substitution; D003001:Cloning, Molecular; D006801:Humans; D008854:Microscopy, Electron; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure*; D016366:Open Reading Frames; D010750:Phosphoproteins / Q000737:chemistry / Q000648:ultrastructure; D017354:Point Mutation; D011392:Proline; D011994:Recombinant Proteins / Q000737:chemistry / Q000648:ultrastructure; D017384:Sequence Deletion; D051843:Synucleins; D013912:Threonine; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D013912:Threonine; D011392:Proline; D000409:Alanine