Peptide WCPFSRSF ameliorates excitotoxicity and elevates synaptic plasticity in glutamate-damaged SH-SY5Y cells by modulating the PI3K/mTOR/EIF4E and BDNF/CREB/TrkB pathways

The purpose of this study was to illustrate the beneficial effects and underlying mechanisms of peptide Trp-Cys-Pro-Phe-Ser-Arg-Ser-Phe (WCPFSRSF) against excitotoxicity by transcriptome analysis combined with western blot in glutamate-treated neuronal cells. Our results demonstrated that WCPFSRSF restored the cell membrane damage induced by glutamate and promoted cell survival in SH-SY5Y cells. The RNA-sequencing analysis illustrated 376 genes (98 upregulated and 278 downregulated) were differentially expressed between the glutamate- and WCPFSRSF-treated cells. Furthermore, RNA-sequencing screening and further western blot results showed that WCPFSRSF regulated cAMP-related signaling and synapse-related function, which further promoted the translation and protein synthesis, followed by cell survival, neurotrophic pathway and long-term memory. The potential mechanisms of WCPFSRSF were related to the Akt/mTOR/EIF4E signaling pathway and CREB/TrkB/BDNF pathway. Taken together, our study demonstrated that WCPFSRSF could be used as a regulator for synaptic plasticity and neurotrophic-related pathway, which provided evidence that WCPFSRSF is a promising therapeutic strategy for neuroprotection and memory enhancement.

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