Epitope mapping and specificity of the anti-α-synuclein monoclonal antibody Syn-1 in mouse brain and cultured cell lines

While α- and β-synuclein largely overlap in their expression in the vertebrate brain, only α-synuclein accumulates in the fibrillar aggregates typical of Parkinson's disease. It is thus critical to have immunological reagents that distinguish between these two protein isoforms. The monoclonal antibody Syn-1 (Transduction Labs) has been frequently used for the specific detection of α-synuclein. In this report, the epitope for Syn-1 is localized within residues 91-99 of human α-synuclein. Sequence differences exist in this domain that account for the specificity of Syn-1 for α- versus β-synuclein. However, Syn-1 also displays reactivity with additional species (∼45 kDa) in brain homogenates from both wild-type and α-synuclein null mice, indicating a potential for cross-reactivity with a protein species that is unrelated to α-synuclein in brain tissue or extracts.