Research Projects

Parkinson’s disease (PD) remained as an unmet medical need, as no drugs are available to stop the disease progression and there is a dire need for the development of disease modifying therapies. While exploring for new molecular targets, our lab has previously identified two alternatively spliced forms of -syn, namely, oxidant-induced generation of 112-syn as well as 41-syn, which is a 41 aa peptide form of -syn in both animal models and human subjects. Though we have studied the downstream effects of the above isoforms, the ulterior role of alternative splicing events in the pathophysiology of PD is not yet clear. Emerging reports indicate that epitopes in the N-and C-terminal region of -syn generate MHC class II peptides on cell surface in PD patients, which in-turn activate cytotoxic T-cells / microglia and enhance the death of dopamine neurons2. Surprisingly, both 41-syn and 112-syn possess altered amino acid sequence at the indicated N and C-terminal regions due to exon skipping and we presume that these splice junctions could contribute to the observed neuroinflammation and dopamine neuron cell death in PD. Hence, developing strategies to mitigate the expression of smaller isoforms of -syn as well as targeting the splice-junctions of -syn isoforms using specific antibodies could provide us with a plausible therapeutic target for disease modifying therapy / development of prognostic marker for PD.