RRC ID 82730
Author Nakamura R, Matsuda A, Higashi Y, Hayashi Y, Konishi M, Saito M, Akizawa T.
Title 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.
Journal Biomolecules
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.
Volume 14(10)
Published 2024-9-29
DOI 10.3390/biom14101234
PII biom14101234
PMID 39456166
PMC PMC11506537
MeSH 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
IF 4.082
Resource
Human and Animal Cells A549