Discovery and characterization of stable and toxic Tau/phospholipid oligomeric complexes. Academic Article uri icon

Overview

abstract

  • The microtubule-associated protein Tau plays a central role in the pathogenesis of Alzheimer's disease. Although Tau interaction with membranes is thought to affect some of its physiological functions and its aggregation properties, the sequence determinants and the structural and functional consequences of such interactions remain poorly understood. Here, we report that the interaction of Tau with vesicles results in the formation of highly stable protein/phospholipid complexes. These complexes are toxic to primary hippocampal cultures and are detected by MC-1, an antibody recognizing pathological Tau conformations. The core of these complexes is comprised of the PHF6* and PHF6 hexapeptide motifs, the latter in a β-strand conformation. Studies using Tau-derived peptides enabled the design of mutants that disrupt Tau interactions with phospholipids without interfering with its ability to form fibrils, thus providing powerful tools for uncoupling these processes and investigating the role of membrane interactions in regulating Tau function, aggregation and toxicity.

publication date

  • November 22, 2017

Research

keywords

  • Phospholipids
  • tau Proteins

Identity

PubMed Central ID

  • PMC5698329

Scopus Document Identifier

  • 85034731597

Digital Object Identifier (DOI)

  • 10.1016/S1090-7807(03)00082-X

PubMed ID

  • 29162800

Additional Document Info

volume

  • 8

issue

  • 1