Five-mer peptides prevent short-term spatial memory deficits in A[beta]25-35-induced Alzheimer's model mouse by suppressing A[beta]25-35 aggregation and resolving its aggregate form

• Published in: Alzheimer's research & therapy 2023-04, Vol.15 (1)
• Main Authors: Nakamura, Rina, Konishi, Motomi, Higashi, Youichirou, Saito, Motoaki, Akizawa, Toshifumi
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid beta-protein; Analysis; Care and treatment; Diagnosis; Neurotoxicity syndromes; Peptides; Prevention; Risk factors
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-023-01229-2

Background The development of drugs for Alzheimer's disease (AD), which is related to the misfolding and aggregation of amyloid-[beta] (A[beta]), is high in demand due to the growing number of AD patients. In this study, we screened 22 kinds of 5-mer synthetic peptides derived from the Box A region of Tob1 protein to find a peptide effective against A[beta] aggregation. Methods A Thioflavin T (ThT) assay was performed to evaluate aggregation and screen aggregation inhibitors. Male ICR mice (6 weeks old) were administered saline, 9 nmol A[beta]25-35, or a mixture of 9 nmol A[beta]25-35 and 9 nmol GSGFK in the right lateral ventricle. Short-term spatial memory was assessed through Y-maze. Microglia cells (BV-)2 cells were plated on 24-well plates (4 x 10.sup.4 cells/well) and incubated for 48 h, and then, the cells were treated with 0.01, 0.05, 0.1, 0.2, or 0.5 mM GSGFK. After incubation for 24 h, bead uptake was evaluated using a laser confocal microscope and Cytation 5. Results We found two kinds of peptides, GSGNR and GSGFK, that were not only suppressed by aggregation of A[beta]25-35 but also resolved the aggregated A[beta]25-35. Results obtained from the Y-maze test on an A[beta]25-35-induced AD model mouse indicated that GSGFK prevents the deficits in short-term memory induced by A[beta]25-35. The effect of GSGFK on phagocytosis in BV-2 cells proved that GSGFK activates the phagocytic ability of microglia. Conclusions In conclusion, 5-mer peptides prevent short-term memory deficit in A[beta]25-35 induced AD model mouse by reducing the aggregated A[beta]25-35. They may also upregulate the phagocytic ability of microglia, which makes 5-mer peptides suitable candidates as therapeutic drugs against AD. Keywords: Alzheimer's disease, Amyloid [beta] peptide, 5-Mer synthetic peptide, Aggregation, ThT assay