Antibodies to alpha synuclein
The application identifies novel fragments of alpha-synuclein in patients with Lewy Body Disease (LBD) and transgenic animal models thereof. These diseases are characterized by aggregations of alpha-synuclein. The fragments have a truncated C-terminus relative to full-length alpha-synuclein. Some fragments are characterized by a molecular weight of about 12 kDa as determined by SDS gel electrophoresis in tricine buffer and a truncation of at least ten contiguous amino acids from the C-terminus of natural alpha-synuclein. The site of cleavage preferably occurs after residue 117 and before residue 126 of natural alpha-synuclein. The identification of these novel fragments of alpha-synuclein has a number of application in for example, drug discovery, diagnostics, therapeutics, and transgenic animals.
1. An antibody that specificalIy binds to and is end- specific for the for the free C-terminus of a fragment of alpha-synuclein, wherein the fragment is amino acids 1-119 or 1-122 of SEQ ID NO: 1; and does not specifically bind to full-length alpha-synuclein, wherein specific binding requires an association constant of the antibody for the fragment of at least 10 7 M −1 .
2. An antibody that specifically binds to and is end-specific for the free N-terminus of a fragment of alpha-synuclein, wherein the fragment amino acids 120-140 or 123-140 of SEQ ID NO: 1; and does not specifically bind to full-length alpha-synuclein, wherein specific binding requires an association constant of the antibody for the fragment of at least 10 7 M −1 .
3. The antibody of claim 1 or claim 2 that is a humanized antibody.
4. The antibody of claim 1 or claim 2 that is a monoclonal antibody.
5. The antibody of claim 1 or claim 2 having human isotype IgGI.