Life Sciences & Biotechnology
Title : | Decoding the role of Pirh2 in dementia of Alzheimer’s type (DAT) related neurodegenerative signaling mechanisms |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Sarika Singh, CSIR-Central Drug Research Institute (CSIR-CDRI), Uttar Pradesh. |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | sarika_singh@cdri.res.in |
Equipments : | Homeothermic Blanket with accessories with trimmer Data visualization system for existing microscope
Liquid Nitrogen Storage Container (for biological samples) |
Details
Executive Summary : | Dementia of Alzheimer type (DAT) is a progressive, fatal neurodegenerative condition characterized by deterioration in cognition, memory and progressive impairment in the ability to carry out the activities of daily living with inclusions of various behavioral and psychological ailments (Jalbert et al, 2008; Jessica et al, 2008). Disease pathology involves extensive neurodegeneration and loss of synaptic connections, resulting in progressive atrophy of the temporal, frontal and parietal lobes of the cortex and hippocampus. It is also characterized by the hallmark deposition of intracellular, filamentous aggregates mainly consisting of hyper-phosphorylated tau (neurofibrillary tangles, NFTs) and extracellular plaques rich in amyloid-β (amyloid plaques) (Ganguly et al, 2017). Amyloid-β produced by the cleavage of the amyloid precursor protein (APP) in endoplasmic reticulum is reported to be critically involve in various deleterious effects on neuronal health and connectivity (Thinakaran and Koo, 2008). Mutations in the genes encoding APP or the presenilin protease enzymes that cleave APP to generate amyloid-β cause early-onset AD, and suggested that amyloid-β metabolism is a central component of AD pathogenesis (Bertram et al., 2010). Such disease related protein aggregates contain ubiquitinated tau and amyloid- β and suggesting the role of protein degradation mechanism like ubiquitin proteasome system (UPS) in disease pathology (Riederer et al, 2011; Sulistio and Heese, 2016) however, limited evidences are available. E3 ubiquitin ligases play regulatory role in proteasome mediated degradation of misfolded or unfolded proteins. Pirh2/Rchy1 is E3 ubiquitin ligase and reported to play diverse role in cancer (Jung et al, 2012) however, its role in cognition remains unexplored. In this proposal we intend to investigate the role of Pirh2 in DAT pathology and related neurodegenerative signaling. |
Total Budget (INR): | 48,00,600 |
Organizations involved