A novel peptide-based tau aggregation inhibitor as a potential therapeutic for Alzheimer's disease and other tauopathies.

ABSTRACT:

Introduction

As aggregation underpins Tau toxicity, aggregation inhibitor peptides may have disease-modifying potential. They are therefore currently being designed and target either the ³⁰⁶VQIVYK³¹¹ aggregation-promoting hotspot found in all Tau isoforms or the ²⁷⁵VQIINK²⁸⁰ aggregation-promoting hotspot found in 4R isoforms. However, for any Tau aggregation inhibitor to potentially be clinically relevant for other tauopathies, it should target both hotspots to suppress aggregation of Tau isoforms, be stable, cross the blood-brain barrier, and rescue aggregation-dependent Tau phenotypes in vivo.

Methods

We developed a retro-inverso, stable D-amino peptide, RI-AG03 [Ac-rrrrrrrrGpkyk(ac)iqvGr-NH2], based on the ³⁰⁶VQIVYK

SUBMITTER: Aggidis A 

PROVIDER: S-EPMC11567856 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature