cis-phosphorylated microtubule-associated protein tau (cis-p-tau)

cis-phosphorylated microtubule-associated protein tau (cis-p-tau) is a pathogenic conformational isomer of the tau protein, specifically phosphorylated at the Threonine 231 (Thr231) residue. In healthy neurons, tau exists primarily in the trans-conformation, which facilitates microtubule assembly and axonal stability. However, under pathological conditions such as oxidative stress or traumatic injury, tau undergoes a conformational shift to the cis-isomer, which is neurotoxic, resistant to degradation, and prone to forming aggregates. This cis-conformation is an early driver of neurodegeneration, appearing before the formation of neurofibrillary tangles in Alzheimer's disease, traumatic brain injury (TBI), and chronic traumatic encephalopathy (CTE). The accumulation and prion-like spreading of cis-p-tau, known as cistauosis, leads to the collapse of the axonal cytoskeleton and eventual neuronal apoptosis. Therapeutic interventions, including conformation-specific monoclonal antibodies like PNT001, aim to neutralize cis-p-tau to halt disease progression and restore neuronal function.

Other names

cis-pT231-taucis-phosphorylated tau proteincis-p-taupathogenic cis-taucis-phosphorylated Thr231-tau

Neutralization of toxic cis-p-tau conformers to prevent aggregation and prion-like spreading (cistauosis), thereby protecting axonal integrity and preventing neuronal apoptosis.