Life Sciences & Biotechnology
Title : | Deciphering the role of amyloidogenic cofilins in the brain under pathological conditions including energy inhibition and oxidative stress: relevance to Alzheimer's Disease |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Neurobiology |
Principal Investigator : | Dr. Pankaj Goyal, Central University Of Rajasthan, Ajmer, Rajasthan |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | pankaj_bio@curaj.ac.in |
Equipments : | Bacterial Incubator ad shaker
Ultra Low temperature freezer
Protein Transfer Device and accessories |
Details
Executive Summary : | Amyloid formation, a protein or peptide, is a key factor in neurodegenerative diseases like Alzheimer's and Parkinson's. It impairs cellular functions, leading to cell death. Early signs and symptoms of neurodegenerative diseases, such as metabolic decline, may contribute to amyloid formation. The molecular mechanism of amyloid cytotoxicity in neurodegeneration and dementia remains elusive. Early defects in glucose transporters, glycolysis, increased serum insulin levels, hypometabolism, mitochondrial homeostasis, and increased degenerating neurons, caspase-3, and DNA fragmentation have been reported in AD modeled rat brains. Cofilin, an actin-dynamizing protein, regulates actin cytoskeleton dynamics by polymerizing or depolymerizing actin in eukaryotic cells. Studies have shown that actin-cofilin rods play a role in neurodegenerative diseases, such as degeneration of neurites and loss of synapses. ATP depletion, oxidative stress, Amyloid-ß (Aß), and mitochondrial dysfunction induce the formation of actin-cofilin rods that recruit the phosphorylated microtubule-associated protein (Tau) to form neurofibrillary tangles in Alzheimer's pathology. Cofilin exists in monomeric and oligomeric forms, and its potential to cross-seed and promote the aggregation of other globular proteins and amino acids suggests its role in amyloid-linked diseases. This project proposes that pathophysiological conditions such as hypometabolism and oxidative stress trigger cofilin amyloid formation and/or induce cofilin oligomerization, leading to mitochondrial dysfunctions leading to neurodegenerative diseases like Alzheimer's. |
Co-PI: | Dr. Senthilkumar Sivanesan, Saveetha Institute Of Medical And Technical Sciences, Chennai,Tamil Nadu-602105 |
Total Budget (INR): | 67,91,224 |
Organizations involved