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

被引：0

作者：

Nakamura, Rina ^{[1
,2
]}

Matsuda, Akira ^{[3
]}

Higashi, Youichirou ^{[1
]}

Hayashi, Yoshihiro ^{[2
,4
]}

Konishi, Motomi ^{[5
]}

Saito, Motoaki ^{[1
]}

Akizawa, Toshifumi ^{[1
,2
]}

机构：

[1] Kochi Univ, Kochi Med Sch, Dept Pharmacol, Oko Cho, Kochi 7838505, Japan

[2] O Force Co Ltd, 3454 Irino Kuroshio Cho, Kochi 7891931, Japan

[3] Hiroshima Int Univ, Fac Pharmaceut Sci, Lab Med & Biochem Anal, 5-1-1 Hirokoshingai, Hiroshima 7370112, Japan

[4] Kochi Univ, Equipment Support Planning Off, Oko Cho, Kochi 7838505, Japan

[5] Setsunan Univ, Fac Pharmaceut Sci, Dept Integrat Pharm, 45-1 Nagaotoge Cho, Hirakata, Osaka 5730101, Japan

来源：

BIOMOLECULES | 2024年 / 14卷 / 10期

基金：

日本学术振兴会;

关键词：

Alzheimer's disease; amyloid-beta peptide; YS-RD11; peptide; aggregation; ThT assay; AMYLOID CASCADE HYPOTHESIS; BETA; DISEASE; PREVENTION; MEMORY; IMPAIRMENT; REDUCTION; PLAQUES;

D O I：

10.3390/biom14101234

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-beta (A beta), 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 A beta 25-35 to identify an applicable peptide for clinical use for AD treatment and prevention. Suppression and aggregate resolution activities of YS-peptides against A beta 25-35 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 A beta 25-35-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.

引用

页数：14

共 53 条

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