Identifying the Pathological Domain of Alpha- Synuclein as a Therapeutic for Parkinson’s Disease.

Identifying the Pathological Domain of Alpha- Synuclein as a Therapeutic for Parkinson’s Disease.

Publication date: May 11, 2019

Alpha-synuclein is considered the major pathological protein associated with Parkinson’s disease, but there is still no effective immunotherapy which targets alpha-synuclein. In order to create a safer and more effective therapy against PD, we are targeting an epitope of alpha-synuclein rather than full-length alpha-synuclein. We have selected several antigenic domains (B-cell epitope) through antigenicity prediction, and also made several recombinant protein fragments from alpha-synuclein upon antigenicity prediction in an E. coli system. We then tested the function of each of the peptides and recombinant fragments in aggregation, their toxicity and antigenicity. We have discovered that the full-length recombinant (aa1-140) can aggregate into oligomers or even fibrils, and fragment aa15-65 can promote the aggregation of aa1-140. It is worth noting that it not only promotes whole protein aggregation, but also self-aggregates as seen by western blotting and silver staining assays. We have tested all candidates on primary neurons for their toxicity and discovered that aa15-65 is the most toxic domain compared to all other fragments. The antibody targeting this domain also showed both anti-aggregation activity and some therapeutic effect. Therefore, we believe that we have identified the most potent therapeutic domain of alpha synuclein as a therapeutic target.

Shen, N., Song, G., Yang, H., Lin, X., Brown, B., Hong, Y., Cai, J., and Cao, C. Identifying the Pathological Domain of Alpha- Synuclein as a Therapeutic for Parkinson’s Disease. 20759. 2019 Int J Mol Sci (20):9.

Concepts Keywords
Antibody Alpha
B Cell Parkin
Epitope Antibody
Fibrils Neuropathology
Immunotherapy Alpha-synuclein
Neurons Medical specialties
Oligomers Lewy body dementia
Parkinson Proteins
Peptides Peripheral membrane proteins
Recombinant Branches of biology
Sci S disease
Silver Staining Immunotherapy
Targeting Domain
Toxicity
Western Blotting

Semantics

Type Source Name
drug DRUGBANK Silver

Original Article

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