Microtubule-associated protein tau aggregate (Tau aggregate)

Microtubule-associated protein tau (MAPT) is a critical neuronal protein that normally binds to and stabilizes microtubules, supporting axonal transport and structural integrity (NIH, 2024). In various neurodegenerative diseases known as tauopathies, tau undergoes pathological changes—including hyperphosphorylation and misfolding—that cause it to detach from microtubules and self-assemble into insoluble aggregates (MDPI, 2024). These aggregates progress from soluble oligomers to paired helical filaments (PHFs) and eventually into large neurofibrillary tangles (NFTs), with the tau repeat domain (MTBR) forming the structural core of these amyloid-like folds (DOI.org, 2022). Pathological tau conformers are known to exhibit "prion-like" properties, spreading between neurons and seeding the misfolding of healthy tau, a process that correlates closely with the progression of cognitive decline and neuronal death (Drug Discovery News, 2024). Therapeutic efforts focus on inhibiting tau aggregation, promoting the clearance of extracellular tau seeds through immunotherapy, or reducing total tau levels using antisense oligonucleotides (UKRI, 2024). Key challenges in targeting these conformers include the intracellular location of most aggregates, the diversity of tau "strains" across different diseases, and the risk of disrupting the essential physiological roles of normal tau (Medical News Today, 2024).

Other names

Neurofibrillary tangleNFTPaired helical filamentPHFTau oligomerPathological tau conformerTau repeat domain aggregateMicrotubule-binding region (MTBR) aggregateTau fibril

Aggregation inhibition, disaggregation of existing filaments, immunotherapy-mediated clearance of extracellular seeds, and reduction of tau protein expression via antisense oligonucleotides.