How short peptides disassemble tau fibrils in Alzheimer's disease.

ABSTRACT: Reducing fibrous aggregates of the protein tau is a possible strategy for halting the progression of Alzheimer's disease (AD)¹. Previously, we found that in vitro, the D-enantiomeric peptide (D-peptide) D-TLKIVWC disassembles ultra-stable tau fibrils extracted from the autopsied brains of individuals with AD (hereafter, these tau fibrils are referred to as AD-tau) into benign segments, with no energy source other than ambient thermal agitation². To consider D-peptide-mediated disassembly as a potential route to therapeutics for AD, it is essential to understand the mechanism and energy source of the disassembly action. Here, we show that the assembly of D-peptides into amyloid-like ('mock-amyloid') fibrils is essential for AD-tau disassembly. These mock-amyloid fibril

SUBMITTER: Hou K 

PROVIDER: S-EPMC12369647 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature