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: shimoke@kansai-u.ac.jp |
| 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.
