An 11-mer Synthetic Peptide Suppressing Aggregation of Aβ25-35 and Resolving Its Aggregated Form Improves Test Performance in an Aβ25-35-Induced Alzheimer's Mouse Model

Biomolecules. 2024 Sep 29;14(10):1234. doi: 10.3390/biom14101234.

Abstract

There is a high demand for the development of drugs against Alzheimer's disease (AD), which is related to the misfolding and aggregation of Amyloid-β (Aβ), due to the increasing number of patients with AD. In our present study, we aimed to assess the aggregation inhibitory effect of various synthetic YS-peptides on Aβ25-35 to identify an applicable peptide for clinical use for AD treatment and prevention. Suppression and aggregate resolution activities of YS-peptides against Aβ25-35 were evaluated using a Thioflavin T assay and scanning electron microscopy (SEM). Structure-activity relationship studies revealed that YS-RD11 (RETLVYLTHLD) and YS-RE16 (RETLVYLTHLDYDDTE) showed suppression and aggregate-resolution activities. The effect of YS-peptides on phagocytosis in microglial cells (BV-2 cells) demonstrated that YS-RD11 and YS-RE16 activated the phagocytic ability of microglia. In the Aβ25-35-induced AD mouse model, YS-RD11 prevented and improved the deficits in short-term memory. In conclusion, YS-RD11 is a suitable candidate therapeutic drug against AD and uses a strategy similar to that used for antibodies.

Keywords: Alzheimer’s disease; ThT assay; YS-RD11 peptide; aggregation; amyloid-β peptide.

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides* / metabolism
  • Animals
  • Cell Line
  • Disease Models, Animal*
  • Male
  • Mice
  • Microglia / drug effects
  • Microglia / metabolism
  • Peptide Fragments* / pharmacology
  • Peptides / chemistry
  • Peptides / pharmacology
  • Phagocytosis / drug effects
  • Protein Aggregates / drug effects
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • amyloid beta-protein (25-35)
  • Peptide Fragments
  • Protein Aggregates
  • Peptides