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Description

Microtubule-associated protein tau (UniProt: P10636, also known as Neurofibrillary tangle protein, Paired helical filament-tau, PHF-tau) is encoded by the MAPT (MAPTL, MTBT1, TAU) gene (Gene ID: 4137) in human. Tau proteins are mostly found in the axons of neurons, in the cytosol and in association with plasma membrane components. Normally, Tau promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The localization of Tau protein in the Alzheimer s disease (AD) brain is markedly abnormal and may contribute to neuronal dysfunction. In AD, normal soluble cytoskeletal elements, such as Tau and neurofilaments, are transformed into insoluble paired helical filaments (PHFs). This is linked to the post-translational change in Tau, primarily its hyperphosphorylation by a number of protein kinases. In its non-phosphorylated state, Tau promotes rapid and extensive microtubule (MT) polymerization. A significant consequence of Tau hyperphosphorylation in AD is a reduction in its ability to bind microtubules and promote microtubule assembly. Hyperphosphorylated Tau may contribute to a destabilized microtubule network, impaired axonal transport, and ultimately result in NFT formation and neuronal death.

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