alexa Mechanisms of Neurotrophic Activities via Low-molecular-weight Compounds: Post-transcriptional Regulation in PC12 Cells and Neurons | OMICS International | Abstract
ISSN: 2167-065X

Clinical Pharmacology & Biopharmaceutics
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Review Article

Mechanisms of Neurotrophic Activities via Low-molecular-weight Compounds: Post-transcriptional Regulation in PC12 Cells and Neurons

Hiroki Maruoka1,2 and Koji Shimoke1*
1Department of Life Science and Biotechnology, Faculty of Chemistry, Materials, and Bioengineering and Strategic Research Base, Kansai University, Japan
2Technology Research Laboratory, KURABO, Japan
Corresponding Author : Dr. Koji Shimoke
Department of Life Science and Biotechnology
Faculty of Chemistry, Materials
and Bioengineering and Strategic Research Base
Kansai University, 3-3-35, Yamate-cho
Suita, Osaka 564-8680, Japan
Tel: +81-6-6368-0853
Fax: +81-6-6330-3770
E-mail: [email protected]
Received January 10, 2013; Accepted February 20, 2013; Published February 27, 2013
Citation: Maruoka H, Shimoke K (2013) Mechanisms of Neurotrophic Activities via Low-molecular-weight Compounds: Post-transcriptional Regulation in PC12 Cells and Neurons. Clin Pharmacol Biopharm S1:003. doi:10.4172/2167-065X.S1-003
Copyright: © 2013 Maruoka H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Recently, it was reported that some low-molecular-weight compounds mimic neurotrophic activities including neurite outgrowth and neuroprotection. Carnosic acid (CA) promotes neurite outgrowth through the activation of Nrf2 in a model of neuron PC12 cells. CA also protects neurons from oxidative stress via the keap/Nrf2 transcriptional pathway. Luteolin induces neurite outgrowth via MAPK, PKC, and cAMP/PKA signaling pathways. In addition, luteolin protects PC12 cells from serum withdrawal-induced oxidative stress. Forskolin-induced neurite outgrowth is mediated by the activation of the PKA signaling pathway, and this PKAmediated neurite outgrowth is achieved by the expression of Nur77 in PC12 cells. In addition, a low concentration of forskolin is closely related to the cAMP-induced protective function against L-DOPA-induced cytotoxicity. The post-transcriptional regulation of gene expression including microRNAs and the acetylation of non-histone protein plays critical roles in neurotrophic activities. Recently, it was revealed that miR-132 modulates luteolin-induced neurite outgrowth via cAMP/PKA- and MAPK-dependent CREB signaling pathways in PC12 cells. Moreover, it has been reported that acetylated Nrf2 binds to the transcriptional activator, CBP/p300 directly, and that Nur77 is acetylated in vivo and in vitro by CBP/p300. The modulation of miR-132 and acetylation of Nrf2 and Nur77 by CBP/p300 may constitute a similar novel regulatory mechanism for low-molecular-weight compounds with neurotrophic activities.

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