AUTOANTIGENS IN PARKINSON'S DISEASE

Parkinson’s disease (PD) is a debilitating movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Little is known about the role of autoimmunity in PD pathogenesis. This thesis examines the role of two autoantigens, α-synuclein and the stress inducible phosphoprotein 1(STIP1) in PD. α-synuclein has been widely implicated in PD pathogenesis while STIP1’s role in PD remains to be determined. Here, we performed a detailed characterization of autoantibodies and antigen-specific T cells using an overlapping peptide library of the full-length α-synuclein and STIP1 protein. Fine epitope determination revealed PD-specific B cell epitopes against both autoantigens. STIP1 was also demonstrated to be neuroprotective against staurosporine-induced neurotoxicity in human dopaminergic neurons derived from induced pluripotent stem cells. Our clinical and neuro-immunological studies thus highlight the potential of the STIP1 co-chaperone as an endogenous neuroprotective agent in PD, and suggest that autoimmune mechanisms may contribute to the underlying pathogenesis via the production of autoantibodies.

Author dc:creator

• TAN SU YI, JOLENE

• Parkinson's Disease, Autoimmunity, Autoantibodies, Antigen-specific T cells, STIP1, Neurodegenerative Diseases