Life Sciences & Biotechnology
Title : | Targeting alternatively spliced isoforms of alpha-synuclein as a disease modifying therapy for Parkinson's disease |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Immunology |
Principal Investigator : | Dr. shasi Vardhan Kalivendi, CsIR- Indian Institute of Chemical Technology, Hyderabad, Telangana |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | kalivendi@iict.res.in |
Details
Executive Summary : | 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 alpha-syn, namely, oxidant-induced generation of 112-syn as well as 41-syn, which is a 41 aa peptide form of alpha-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 alpha-syn generate MHC class II peptides on cell surface in PD patients, which in-turn activate cytotoxic T-cells or 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 alpha-syn as well as targeting the splice-junctions of alpha-syn isoforms using specific antibodies could provide us with a plausible therapeutic target for disease modifying therapy or development of prognostic marker for PD. |
Total Budget (INR): | 62,19,920 |
Organizations involved