Original Research Article
Signal transduction pathways involved in PPARβ/δ-induced neuronal differentiation
Article first published online: 25 APR 2011
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 226, Issue 8, pages 2170–2180, August 2011
How to Cite
D'Angelo, B., Benedetti, E., Di Loreto, S., Cristiano, L., Laurenti, G., Cerù, M.P. and Cimini, A. (2011), Signal transduction pathways involved in PPARβ/δ-induced neuronal differentiation. J. Cell. Physiol., 226: 2170–2180. doi: 10.1002/jcp.22552
- Issue published online: 25 APR 2011
- Article first published online: 25 APR 2011
- Accepted manuscript online: 6 DEC 2010 12:00AM EST
- Manuscript Accepted: 9 NOV 2010
- Manuscript Received: 21 JUL 2010
- Italian Ministry of University and Research (MIUR)
Neuroblastomas are pediatric tumors originating from neuroblasts in the developing peripheral nervous system. The neurotrophin brain-derived neurotrophic factor (BDNF) is a key regulator of survival and differentiation of specific neuronal populations in the central and peripheral nervous system. Patients whose neuroblastoma tumors express high levels of BDNF and TrkB have an unfavorable prognosis. We have previously reported on the neuronal differentiating activity of peroxisome proliferator-activated receptors (PPAR)β/δ natural and synthetic ligands by modulating BDNF/TrkB pathway, suggesting their potential use as new therapeutic strategies for neuroblastoma. The validation of new therapeutic agents implies the understanding of their mechanisms of action. Herein, we report the effects of activated-PPARβ/δ on signal transduction pathways known to be involved in neuronal differentiation, such as ERK1,2 and BDNF pathways. The results obtained, using also PPARβ/δ silencing, indicating a neuronal differentiating effect PPARβ/δ-dependent through BDNF-P75-ERK1,2 pathways, further support a role for PPARβ/δ in neuronal differentiation and pointing towards PPARβ/δ as a modulator of pathways crucial for neuronal differentiation. These findings open new perspectives in the formulation of potential therapeutic approaches to be used as adjuvant treatment with the standard therapies. J. Cell. Physiol. 226: 2170–2180, 2011. © 2010 Wiley-Liss, Inc.