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 |