PRMT3-Mediated H4R3me2a Promotes Primary Age-Related Tauopathy by Driving Tau Hyperphosphorylation in Neuron.

ABSTRACT: Primary age-related tauopathy (PART) and Alzheimer's disease (AD) both exhibit 3R/4R hyperphosphorylated tau-positive neurofibrillary tangles (NFTs) within the hippocampal-entorhinal system. Notably, PART patients show a higher degree of tau hyperphosphorylation in the entorhinal cortex (EC) than AD, yet the molecular mechanisms driving Aβ-independent tau hyperphosphorylation in PART remain poorly understood. Herein, through transcriptomic profiling of postmortem EC tissues and in vitro and in vivo functional validation, the present study identifies protein arginine methyltransferase 3 (PRMT3) as a critical driver of tau hyperphosphorylation. Mechanistically, PRMT3-mediated tau hyperphosphorylation is dependent on asymmetric dimethylation of histone H4 at arginine 3 (H4R3me2a), which upreg

SUBMITTER: Liu H 

PROVIDER: S-EPMC12302536 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature