G-protein coupled receptors (GPCRs) interacts with Tau protein in Alzheimer's disease.

The pathophysiological scenario of Alzheimer's disease (AD) includes the misfolding and mis-sorting of two cellular proteins: Amyloid-β as plaques and microtubule-associated protein Tau as intracellular neurofibrillary tangles (NFTs). The protein oligomers are the short-lived but, highly reactive species which mediate toxicity, synaptic loss, neurodegeneration and ultimately cognitive decline. Tau oligomers can propagate through various pathway viz. the exosomal pathway, neurotransmission, cell-to-cell junction, bulk endocytosis and receptor-mediated internalization etc. The preparation, isolation and detection of oligomers were of immense importance in the current field for designing therapeutics and diagnostics. Microglia are the prime immune cells in brain which maintain the homeostasis via synaptic surveillance and tissue-remodeling. But, the senescent microglia mediate pro-inflammation, oxidative damage and phagocytosis in diseased brain. The extracellular Tau oligomers were found to interact with microglial purinergic receptor P2Y12 which then led to microglial migration, activation and phagocytosis via various remodeled actin structure. P2Y12 receptor mediates Tau oligomers-induced microglial chemotaxis by localizing with migratory actin structures such as- filopodia, lamellipodia, podosome etc. These beneficial roles of P2Y12 in microglial chemotaxis, actin remodeling and Tau clearance can be intervened as a therapeutic target in AD.