PEPTIDE FRAGMENT OF THYMOSIN β4 INCREASES HIPPOCAMPAL NEUROGENESIS AND FACILITATES SPATIAL MEMORY

초록

Although several studies have suggested the neuroprotective effect of thymosin beta 4 (TB4), a major actin-sequestering protein, on the central nervous system, little is understood regarding the action of N-acetyl-serylas partyl-lysyl-proline (Ac-SDKP), a peptide fragment of TB4 on brain function. Here, we examined neurogenesis-stimulative effect of Ac-SDKP. Intrahippocampal infusion of Ac-SDKP facilitated the generation of new neurons in the hippocampus. Ac-SDKP-treated mouse hippocampus showed an increase in beta-catenin stability with reduction of glycogen synthase kinase-3 beta (GSK-3 beta) activity. Moreover, inhibition of vascular endothelial growth factor (VEGF) signaling blocked Ac-SDKP-facilitated neural proliferation. Subchronic intrahippocampal infusion of Ac-SDKP also increased spatial memory. Taken together, these data demonstrate that Ac-SDKP functions as a regulator of neural proliferation and indicate that Ac-SDKP may be a therapeutic candidate for diseases characterized by neuronal loss. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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