Microtubule-associated protein tau, misfolded and aggregated form (tau (aggregated))

Misfolded and aggregated tau protein refers to the pathological forms of the microtubule-associated protein tau that have undergone abnormal post-translational modifications (notably hyperphosphorylation and truncation), resulting in its detachment from microtubules and subsequent assembly into insoluble aggregates such as oligomers, paired helical filaments, and neurofibrillary tangles[1][5][7]. Aggregated tau loses its physiological function in stabilizing microtubules, disrupts neuronal cytoskeleton, impairs axonal and synaptic function, and exerts neurotoxic effects by promoting dysfunction and death of neurons[4][9]. The process of tau aggregation is a hallmark of a class of neurodegenerative diseases called tauopathies, most notably Alzheimer’s disease, as well as other disorders like frontotemporal dementia and progressive supranuclear palsy[8][9]. The molecular dynamics of tau aggregation are influenced by post-translational modifications, truncations, interactions with acidic and membrane surfaces, and environmental conditions such as pH and ionic strength[1][3][4]. Due to its central role in neurodegeneration, misfolded and aggregated tau is a major therapeutic target for interventions ranging from aggregation inhibitors to immunotherapies, though clinical translation faces challenges in selectivity, efficacy, and safety[9].

Other names

Aggregated tau proteinHyperphosphorylated tauTau neurofibrillary tanglesPaired helical filament tauMisfolded tauTau oligomers

Inhibition of tau phosphorylation (kinase inhibitors); Inhibition of tau aggregation (aggregation inhibitors); Enhancement of tau clearance (immunotherapy, proteostasis modulators); Stabilization of native tau conformation; Suppression of tau misfolding and oligomerization