MAPT

Gene Number: 4137

Location: 17q21.31

Key Functions: Microtubule stabilization, neuronal structure maintenance, axonal transport regulation, cytoskeletal organization, and neurodegeneration prevention

MAPT encodes microtubule-associated protein tau, a fundamental structural protein in neurons that binds to and stabilizes microtubules—the intracellular scaffolds responsible for maintaining cell shape, polarity, and the directed transport of organelles and vesicles along axons and dendrites. Tau ensures the integrity of axonal transport, facilitating the movement of mitochondria, synaptic vesicles, and other essential components required for synaptic communication and neuronal survival.

Tau’s activity is dynamically modulated by post-translational modifications—most notably phosphorylation. Under physiological conditions, reversible phosphorylation regulates tau’s affinity for microtubules and its involvement in axonal transport. However, in pathological states, hyperphosphorylation of tau reduces its microtubule-binding ability, leading to microtubule destabilization and the accumulation of soluble tau oligomers and insoluble paired helical filaments (PHFs). These filaments aggregate into neurofibrillary tangles (NFTs), one of the key histopathological hallmarks of Alzheimer’s disease, frontotemporal lobar degeneration (FTLD-tau), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD).

In addition to its structural role, tau is increasingly recognized as a signaling molecule involved in neuronal stress response, DNA protection, and synaptic regulation. Its mislocalization from axons to the somatodendritic compartment during disease progression disrupts intracellular communication, promotes oxidative stress, and triggers inflammatory and apoptotic cascades.

Overall, MAPT represents a nexus point between cytoskeletal regulation and neurodegenerative pathology, underscoring the importance of tau protein balance in preserving neuronal structure, function, and longevity.