Binding of Pro-Inflammatory Proteins S100A8 or S100A9 to Amyloid-β Peptide Suppresses Its Fibrillation.

ABSTRACT: Human serum albumin (HSA) is a natural depot of amyloid-β peptide (Aβ), a key player in Alzheimer's disease (AD). HSA and pro-inflammatory Ca²⁺-binding proteins S100A8 and S100A9 are involved in Aβ metabolism and its deposition in the brain, serving as probable triggers and therapeutic targets in AD, but their interplay with regard to Aβ binding/fibrillation is unclear. To this end, here we explore the in vitro binding of Ca²⁺-bound S100A8 or S100A9 to monomeric Aβ and the influence of the S100 proteins on Aβ fibrillation. The equilibrium dissociation constants of the complexes of dimeric S100A8/S100A9 with Aβ40/42 estimated by biolayer interferometry are 1-5 µM. S100A8 and S100A9 interfere with HSA binding to Aβ. Thioflavin T assay and electron microscopy data show t

SUBMITTER: Litus EA 

PROVIDER: S-EPMC11939996 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature