title: Signal transduction pathways involved in PPARβ/δ-induced neuronal differentiation.
abstract: 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.
authors.affiliation: Department of Basic and Applied Biology, University of L'Aquila, Italy.
authors.forename: B
authors.initials: B
authors.lastname: D'Angelo
authors.forename: E
authors.initials: E
authors.lastname: Benedetti
authors.forename: S
authors.initials: S
authors.lastname: Di Loreto
authors.forename: L
authors.initials: L
authors.lastname: Cristiano
authors.forename: G
authors.initials: G
authors.lastname: Laurenti
authors.forename: M P
authors.initials: MP
authors.lastname: Cerù
authors.forename: A
authors.initials: A
authors.lastname: Cimini
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D047494:PPAR delta; D048068:PPAR-beta; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3