Microtubule-associated protein tau (phosphorylated at Threonine 212) (p-Thr212 Tau)

Microtubule-associated protein tau (phosphorylated at Threonine 212) is a pathological post-translational modification of the MAPT protein (UniProt: P10636). Under physiological conditions, tau stabilizes microtubules, but hyperphosphorylation at Thr212 promotes its detachment and subsequent aggregation into toxic species (PubMed: 11518741). This specific phosphorylation is catalyzed by several proline-directed kinases, most notably Glycogen Synthase Kinase-3 beta (GSK-3β) and Cyclin-dependent kinase 5 (CDK5) (PubMed: 25154368). The accumulation of p-Thr212 tau is strongly associated with the formation of paired helical filaments and neurofibrillary tangles, which are hallmarks of Alzheimer's disease and other tauopathies (PubMed: 32719768). As a therapeutic target, researchers focus on inhibiting these upstream kinases or utilizing monoclonal antibodies to facilitate the clearance of phosphorylated tau. Furthermore, p-Thr212 has emerged as a highly sensitive fluid biomarker in cerebrospinal fluid and plasma for the early detection and staging of Alzheimer's disease (PubMed: 33230385). Clinical challenges include the high degree of similarity between pathological and functional tau, necessitating high specificity in drug design to avoid disrupting normal axonal transport. Successful modulation of this target aims to restore microtubule stability and mitigate neurodegeneration in the aging brain.

Other names

pT212Phospho-tau (Thr212)MAPT pT212Tau pThr212p-tau212

Inhibition of upstream kinases such as GSK-3β and CDK5 to prevent phosphorylation at the Thr212 site, or the use of monoclonal antibodies to target and facilitate the clearance of hyperphosphorylated tau aggregates from the brain.