title: A panel of epitope-specific antibodies detects protein domains distributed throughout human alpha-synuclein in Lewy bodies of Parkinson's disease.
abstract: To facilitate studies of the normal biology of alpha-synuclein, a member of a family of neuronal proteins of unknown function, and to elucidate the role of alpha-synuclein pathologies in neurodegenerative diseases, we generated and characterized a panel of anti-synuclein antibodies. Here we demonstrate that these antibodies recognize defined epitopes spanning the entire length of human alpha-synuclein, and that some of these antibodies also cross-react with zebra finch and rodent synucleins. Since alpha-synuclein has been reported to be a major component of Lewy bodies (LBs) in Parkinson's disease (PD), dementia with LBs and common variants of Alzheimer's disease, we performed immunohistochemical studies showing that these antibodies label numerous LBs in the PD substantia nigra, thereby localizing protein domains throughout human alpha-synuclein in LBs. Taken together, our data indicate that this panel of antibodies can be exploited to probe the normal biology of alpha-synuclein as well as the role of pathological forms of this protein in PD and related neurodegenerative synucleinopathies.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-4283, USA.
authors.forename: B I
authors.initials: BI
authors.lastname: Giasson
authors.forename: R
authors.initials: R
authors.lastname: Jakes
authors.forename: M
authors.initials: M
authors.lastname: Goedert
authors.forename: J E
authors.initials: JE
authors.lastname: Duda
authors.forename: S
authors.initials: S
authors.lastname: Leight
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: V M
authors.initials: VM
authors.lastname: Lee
mesh_terms: D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D003429:Cross Reactions; D018604:Epitope Mapping; D006801:Humans; D016631:Lewy Bodies / Q000737:chemistry* / Q000276:immunology; D008297:Male; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000502:physiology; D010300:Parkinson Disease / Q000276:immunology*; D013378:Substantia Nigra; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein