CRMP2-derived peptide ST2-104 (R9-CBD3) protects SH-SY5Y neuroblastoma cells against Aβ25-35-induced neurotoxicity by inhibiting the pCRMP2/NMDAR2B signaling pathway

In this study we investigated the effects of ST2-104 on SH-SY5Y neuroblastoma cells stimulated by Aβ25-35. To induce neurotoxicity, SH-SY5Y cells were incubated with Aβ25-35, the shortest toxic fragment of Aβ. CRMP2 expression was manipulated by knockdown or overexpression of CRMP2 before ST2-104 treatment to further explore if the pCRMP2/NMDAR2B signaling pathway is involved in the action of the ST2-104 peptide. The results show that ST2-104 significantly enhanced cell viability, inhibited cell apoptosis, decreased LDH release, suppressed the expression of the pCRMP2 protein, disrupted pCRMP2/NMDAR2B interaction, inhibited Aβ25-35-induced NMDAR currents, and decreased intracellular Ca2+ levels. The effects of ST2-104 was abolished by overexpression of CRMP2 and intensified by knockdown of CRMP2 in SH-SY5Y cells. Taken together, our results support ST2-104 as a possible biologic therapeutic in the face of Aβ25-35-induced injury via the inhibition of the pCRMP2/NMDAR2B signaling pathway.
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research