Fibrillization of Human Tau Is Accelerated by Exposure to Lead via Interaction with His-330 and His-362

摘要

BackgroundNeurofibrillary tangles, mainly consisted of bundles of filaments formed by the microtubule-associated protein Tau, are a hallmark of Alzheimer disease. Lead is a potent neurotoxin for human being especially for the developing children, and Pb²⁺ at high concentrations is found in the brains of patients with Alzheimer disease. However, it has not been reported so far whether Pb²⁺ plays a role in the pathology of Alzheimer disease through interaction with human Tau protein and thereby mediates Tau filament formation. In this study, we have investigated the effect of Pb²⁺ on fibril formation of recombinant human Tau fragment Tau244–372 and its mutants at physiological pH.