Research

Life Sciences & Biotechnology

Title :

Homeostatic benefits and drawbacks of perinuclear positioning of Lewy Body like filamentous inclusions of α-Synuclein

Area of research :

Life Sciences & Biotechnology

Focus area :

Cell Biology

Principal Investigator :

Dr. Swasti Raychaudhuri, CSIR- Centre For Cellular And Molecular Biology (CSIR–CCMB), Hyderabad, Telangana

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Details

Executive Summary :

Protein quality control (PQC) has been facilitated by sequestration into inclusion bodies (IBs), which accumulate misfolded proteins for degradation or quarantine to limit interactions with other cellular proteins. Amyloid IBs are common in neurodegenerative diseases and play both homeostatic and non-homeostatic roles. The perinucleus is a preferred site for localizing misfolding-prone amyloids into IBs, suggesting cells enjoy more homeostatic benefits than costs. Researchers have developed models where amyloidogenic α-Synuclein is confined into two perinuclear IBs, offering unique homeostatic benefits. They plan to investigate the location-specific homeostatic advantages and disadvantages of amyloid-IBs, examining whether the biogenesis of perinuclear IBs is a spontaneous outcome of efficient protein translation or if cells secure strategic benefits from abundant chaperones and degradation machines at the perinucleus. The goal is to delocalize α-Synuclein IBs from the perinucleus to estimate the altered homeostatic benefit to cost ratio. This work will provide insight into the purpose of spatial distribution of homeostatic IBs and the underlying mechanism of proteotoxicity triggered by amyloid-aggregation of α-Synuclein.

Co-PI:

Dr. Mandar V Deshmukh, CSIR- Centre For Cellular And Molecular Biology (CSIR–CCMB), Hyderabad, Telangana-500007

Total Budget (INR):

60,79,088

Organizations involved