Five-mer peptides, GSGFK and GSGNR suppress the aggregation of Aβ25-35 and resolve its aggregate form

Abstract

Abstract Background The development of drugs for Alzheimer’s disease (AD), which is related to the misfolding and aggregation of Amyloid-β (Aβ), 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 Aβ aggregation. Methods A Thioflavin T (ThT) assay was performed to evaluate aggregation and screening aggregation inhibitor. Six weeks male ICR mice were administered of saline, 9 nmol Aβ25–35, or a mixture of 9 nmol Aβ25–35 and 9 nmol GSGFK in the right lateral ventricle. The short-term spatial memory assessed using Y-maze. The BV-2 cells were harvested into 24-well plates (4 × 104 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 of 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, were not only suppressed aggregation of Aβ25–35 but also resolved the aggregated Aβ25–35. Results obtained from the Y-maze test on an Aβ25-35-induced AD mouse model indicated that GSGFK prevents the deficits in short-term memory induced by Aβ25–35. The effect of GSGFK on phagocytosis in microglia cells (BV-2 cells) proved that GSGFK activates the phagocytic ability of microglia. Conclusions In conclusion, 5-mer peptides prevent short-term memory deficit in Aβ25–35 induced AD mouse model by reducing the aggregated Aβ25–35. They may also upregulate the phagocytic ability of microglia, which makes 5-mer peptides suitable candidates as therapeutic drugs against AD.