N-Amination Converts Amyloidogenic Tau Peptides into Soluble Antagonists of Cellular Seeding.

ABSTRACT: The spread of neurofibrillary tangles composed of tau protein aggregates is a hallmark of Alzheimer's and related neurodegenerative diseases. Early oligomerization of tau involves conformational reorganization into parallel β-sheet structures and supramolecular assembly into toxic fibrils. Despite the need for selective inhibitors of tau propagation, β-rich protein assemblies are inherently difficult to target with small molecules. Here, we describe a minimalist approach to mimic the aggregation-prone modules within tau. We carried out a backbone residue scan and show that amide N-amination completely abolishes the tendency of these peptides to self-aggregate, rendering them soluble mimics of ordered β-strands from the tau R2 and R3 domains. Several N-amino peptides (NAPs) inhibit tau fibr

SUBMITTER: Makwana KM 

PROVIDER: S-EPMC9035343 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature