Cytoskeletal proteins regulates Tau protein in Alzheimer's disease

Cytoskeletal proteins, particularly microtubules and actin, play critical roles in maintaining neuronal structure, transport, and function. In Alzheimer's disease (AD), the Tau protein, which normally stabilizes microtubules, becomes hyperphosphorylated and forms neurofibrillary tangles, leading to Tauopathies. This pathological change disrupts microtubule dynamics, axonal transport, and overall neuronal integrity. The cytoskeletal proteins like actin, tubulin, MAPs, ankyrin, gelsolin, vimentin, drebrin, septins, cofilin, spectrin, intermediate filaments and Tau role and function in Alzheimer's disease. Cross-talk between microtubules and actin further exacerbates Tau pathology, contributing to synaptic dysfunction, oxidative stress, and neuronal degeneration and dysregulation accelerates neurodegenerative processes, and Tauopathies. Tau pathology impairs synaptic plasticity by disrupting both actin and microtubule cytoskeletons, leading to dendritic spine loss, synaptic failure, and memory impairment. Compounds that prevent tau hyperphosphorylation or promote its dephosphorylation (e.g., GSK-3β inhibitors) may help stabilize microtubules. Cytoskeletal dysfunction is associated with oxidative stress. Compounds that reduce oxidative stress could protect the cytoskeleton from further damage. Since inflammation exacerbates tau pathology and cytoskeletal breakdown, targeting neuroinflammation may have protective effects on cytoskeletal integrity.