cis-phosphorylated Threonine 231-Proline 232 tau (cis-pT231 tau) (cis-pT231 tau)

The cis-phosphorylated Thr231–Pro232 epitope of tau (cis-pT231 tau) is a specific, pathogenic conformational state of the microtubule-associated protein tau that serves as an early driver of neurodegeneration. Under normal conditions, the prolyl isomerase Pin1 maintains tau in a functional trans-conformation, but stress or injury triggers the formation of the toxic cis-isomer (Lu et al., Nature, 2012). This cis-conformation is unable to promote microtubule assembly, is resistant to dephosphorylation, and spreads between neurons, a process termed "cistosis" (Kondo et al., Nature, 2015). It is found in the brains of patients with Alzheimer's disease, traumatic brain injury (TBI), and chronic traumatic encephalopathy (CTE) long before traditional tau tangles appear (Albensi, Cells, 2023). Therapeutic strategies focus on monoclonal antibodies, such as PNT001, which specifically target and neutralize the cis-pT231 epitope while sparing the functional trans-isomer (Pinteon Therapeutics, 2023). By neutralizing this toxic species, these drugs aim to halt the progression of neurodegeneration and preserve cognitive function in patients. This target represents a shift toward precision medicine in neurology, focusing on specific protein conformations rather than total protein levels.

Other names

cis-p-taucis-pT231cis-phosphorylated taucis-pT231 epitopecis-pT231-tau

Passive immunotherapy using monoclonal antibodies to selectively bind and neutralize the pathogenic cis-conformation of phosphorylated tau, preventing its neurotoxic effects and spreading.