Dr. Vijay Rangachari

Chemistry and Biochemistry

University of Southern Mississippi

Title: “Proteins in Neurodegenerative Pathologies: Disorder, Aggregation and Phase Separation”

Abstract: Neurodegenerative pathologies such as Alzheimer’s (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) involve loss of neurons caused by proteins that form toxic pathogenic aggregates called, ‘amyloids’. Many amyloid forming proteins fall in the class of ‘intrinsically disordered proteins’ (IDPs) that lack well-defined structure. Amyloid formation could be heterogenous with a variety of different aggregates with different protein conformation and shapes, which have lately come to define clinical phenotypes observed among neurodegenerative disease patients. While amyloid formation and deposition involves largely an irreversible transition from a liquid to solid phase, a new realm of dynamics involving liquid-to-liquid phase transitions by IDPs have emerged recently. In addition to neurogenerative pathologies, liquid-liquid phase separation (LLPS) by disordered proteins containing low complexity domains are emerging as a novel cellular mechanism for stress-response with the formation of membrane-less organelles. Our work on many IDPs and amyloid proteins fall into this broad area of protein dynamics and functions, and the presentation will demonstrate potentially new insights into roles of IDPs in both norm and pathology.