Life Sciences & Biotechnology
Title : | Exploring Potential Neurodegenerative Disease Therapy with T177I SNP Mutation in Human Peroxiredoxin 6: A Structural and Functional Assessment |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Rahaman Hamidur, Manipur University, Imphal, Manipur |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | hamidur2006@gmail.com |
Equipments : | UV-Visible Spectrophotometer |
Details
Executive Summary : | Peroxiredoxin 6 (Prdx6) is a peroxidase that detoxifies reactive oxygen species and aids in phospholipid biosynthesis. It is highly conserved and expressed globally. Post-translational modifications, such as oxidation, phosphorylation, and acetylation, can induce conformational changes and regulate Prdx6 function. One such modification is the phosphorylation of the Thr177 residue of Prdx6, which alters enzyme conformation and gains additional aiPLA? activity within the cytosol without affecting its peroxidase activity. A naturally occurring nsSNP (Thr177Ile) has been reported at this phosphorylation site, which affects enzyme conformation and function. Recent reports suggest that enhanced expression of Prdx6 increases oxidative stress and aggravates neurodegenerative diseases by activating cytosolic aiPLA? activity through MAP kinase-mediated Prdx6 phosphorylation. The mutant Prdx6, Thr177Ile, is expected to avoid MAP kinase-mediated phosphorylation and no aiPLA? activity at cytosolic pH. This suggests that the Thr177Ile protein might be beneficial for individuals suffering from neurodegenerative diseases, as their antioxidant enzyme Prdx6 would be catalytically active but not a potential risk at higher concentrations due to phosphorylation-mediated gain of aiPLA? activity. Investigating the effect of the Thr177Ile Prdx6 on Wt Prdx6 structure and function using in vitro and in vivo studies is crucial for confirming the mutant protein's beneficial role in evading neurodegeneration. |
Total Budget (INR): | 37,39,579 |
Organizations involved