Microtubule-associated protein tau phosphorylated at Threonine 231 (cis-conformation) (cis-p-tau231)

Microtubule-associated protein tau phosphorylated at Threonine 231 in the cis-conformation (cis-p-tau231) is a specific, pathogenic form of the tau protein that serves as an early driver of neurodegeneration (Zhou et al., Nature, 2012). While tau normally exists in a trans-conformation to stabilize microtubules, phosphorylation at Thr231 followed by the loss of Pin1 isomerase activity leads to the accumulation of the toxic cis-isomer, a process termed "cistauosis" (Kondo et al., Nature, 2015). This cis-conformation is unable to promote microtubule assembly, is resistant to degradation, and is prone to aggregation and prion-like spreading (Albayram et al., Nature Communications, 2017). Therapeutic targeting of cis-p-tau231, primarily through monoclonal antibodies like PNT001, aims to selectively neutralize this toxic species while sparing the functional trans-tau (Pinteon Therapeutics, 2023). By targeting this early "misshaped" protein, researchers hope to intervene in the neurodegenerative cascade before irreversible damage occurs in conditions such as Alzheimer's disease and traumatic brain injury (Ashton et al., Acta Neuropathologica, 2021). The specificity of this target allows for potential disease-modifying effects with reduced impact on the physiological roles of healthy tau protein.

Other names

cis-p-taucis-pT231cis-phosphorylated tauPathogenic cis-taucis-p-tau (Thr231)

Passive immunotherapy using conformation-specific monoclonal antibodies to neutralize and facilitate the clearance of the pathogenic cis-isomer of phosphorylated tau.