Shen_2012_Int.J.Clin.Exp.Pathol_5_900

Cognitive deficits in AD correlate with progressive synaptic dysfunction and loss The Rho family of small GTPases including Rho Rac and Cdc42 has a central role in cellular motility and cytokinesis Acetylcholinesterase inhibitor has been found to protect cells against a broad range of reagents-induced injuries Present studies examined if the effect of HupA on neurite outgrowth in Abeta-treated neuronal cells executed via regulating Rho-GTPase mediated axon guidance relative gene expression Affymetrix cDNA microarray assay followed by real-time RT-PCR and Western Blotting analysis were used to elucidate and analyze the signaling pathway involved in Abeta and HupA's effects The effects of Abeta and HupA on the neurite outgrowth were further confirmed via immunofluorescence staining Abeta up-regulated the mRNA expressions of NFAT5 LIMK1 EPHA1 NTN4 and RAC2 markedly in SH-SY5Y cells Co-incubation of Abeta and HupA reversed or decreased the changes of NFAT5 NTN4 RAC2 CDC42 and SEMA4F HupA treated alone increased NFAT5 LIMK1 NTN4 significantly Following qRT-PCR validation showed that the correlation of the gene expression ratio between microarray and qRT-PCR is significant Western blot result showed that the change of CDC42 protein is consistent with the mRNA level while RAC2 is not The morphological results confirmed that HupA improved or partly reversed the Abeta-induced damage of neurite outgrowth The protective effect of HupA from Abeta induced morphological injury might be correlative to at least partially regulating the network of neurite outgrowth related genes.