Microtubule-associated protein tau (MAPT) aggregate (Tau aggregate)

Pathological β-sheet-rich tau aggregates are insoluble protein assemblies formed by the misfolding and hyperphosphorylation of the microtubule-associated protein tau (MAPT) (Source: UniProt P10636). Under physiological conditions, tau is a highly soluble protein that stabilizes microtubules and facilitates axonal transport; however, in neurodegenerative diseases known as tauopathies, it adopts a cross-β-sheet conformation (Source: NIH National Institute on Aging). These aggregates, which include paired helical filaments (PHFs) and neurofibrillary tangles (NFTs), are a hallmark of Alzheimer's disease and are closely correlated with cognitive decline (Source: Goedert M, et al., Nature, 2017). The aggregates exert neurotoxicity by disrupting cellular homeostasis and can spread through the brain via a prion-like seeding mechanism, where misfolded tau templates the conversion of native tau in neighboring neurons (Source: PubMed PMC6103309). Therapeutic interventions targeting these aggregates include small molecules designed to inhibit fibrillization, monoclonal antibodies that promote microglial clearance or block extracellular seeding, and PET imaging agents used for diagnosis and monitoring (Source: ClinicalTrials.gov). Challenges in targeting these structures include the structural diversity of tau aggregates across different diseases and the need to avoid interfering with the essential biological functions of monomeric tau (Source: Nature Reviews Drug Discovery, 2018).

Other names

Neurofibrillary tanglesPaired helical filamentsPHFsTau fibrilsTau oligomersMisfolded tauStraight filaments

Inhibition of tau aggregation, promotion of aggregate clearance via immunotherapy, and blocking of trans-cellular seeding and spreading.