Neurobiology Group

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive and behavioural impairment. Worldwide 44 million people are known to have AD and its related dementia. Abnormal protein deposits in the brain, such as extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs), characterize AD. The microtubule-associated protein Tau (MAPT) plays a key role in several neurodegenerative diseases, like AD, FTDP-17 and Parkinson’s disease etc. The axonal protein Tau is expressed in the adult human brain as six different isoforms. Due to alternative splicing, two N-terminal inserts and the second repeat (R2) in the C-terminal microtubule-binding domain can be present or absent. Upon hyperphosphorylation, Tau disassembles from microtubule (MT) and self-assembles to form NFTs which consist of straight paired helical filaments (PHFs). Several factors are responsible for triggering under pathological conditions, such as post-translational modifications, oxidative stress, truncation, and metal ions etc.

Our lab is mainly interested to understand the extracellular Tau internalization in astro-microglial system. Our group identified the Phagocytosis of full-length Tau oligomers by Actin-remodeling of activated microglia. Further the α-Linoleic acid modulates phagocytosis of extracellular Tau and induces microglial migration and actin remodeling in Tauopathy. Further, our work involves in channelizing the lipid-based modulators to polarize microglia/ microglial receptor-based (GPCRs-P2Y12 and CX3CR1) targeting mechanisms for better internalization and subsequent degradation of these Tau seeds by employing various cell-based stimulated approaches.