Miguel Bronfman

Investigation

Our interest is centered in understanding the role of PPARs (Peroxisome proliferator activated receptors) in the regulation of cell differentiation and lipid homeostasis in neurons. PPARs are the target of peroxisome proliferators, including hypolipidemic compounds used in the treatment of hyperlipemia, and of the thiazolendione antidiabetic drugs. They are activated by natural fatty acids and their metabolites (eicosanoids) and belong to the subfamily of nuclear receptors that includes the retinoic acid receptors (RARs) and thyroid hormone receptor (TRs). The PPAR subfamily is composed of three distinct subtypes, PPARalpha, PPARbeta and PPARgamma that form heterodimers with the retinoid X receptor (RXR). PPARalpha modulates the pleiotropic effects of peroxisomal proliferators, regulating genes involved in lipid catabolism, whereas PPARgamma affects key pathways in a variety of diseases, including insulin resistance and Syndrome X. PPARbeta is important in controlling other PPARs and in wound healing. PPARs have been best studied in systemic lipid metabolism, being involved in obesity, diabetes and cancer. Much less is known about their role in the nervous system. We have evidence to consider these receptors as potential pharmacological targets in the treatment of neurodegenerative diseases.

Selected References

Author(s)	Title	Date
Andrea V. Leisewitz, Carolina R Urrutia, Gabriela R Martinez, Gloria Loyola, and Miguel Bronfman.	A PPARs cross-talk concertedly commits C6 glioma cells to oligodendrocytes and induces enzymes involved in myelin synthesis. J. Cellular Physiol., 2008, in press.	0
Karen Fuenzalida, Rodrigo Quintanilla, Patricio Ramos, Daniela Piderit, Rodrigo A Fuentealba, Gabriela Martinez, Nibaldo C Inestrosa and Miguel Bronfman.	PPAR gamma up-regulates the Bcl-2 anti-apoptotic protein in neurons and induces mitochondrial stabilization and protection against oxidative stress and apoptosis. J.Biol. Chem., 2	0
Gatica A, Aguilera MC, Contador D, Loyola G, Pinto CO, Amigo L, Tichauer JE, Zanlungo S, Bronfman M .	P450 CYP2C epoxygenase and CYP4A omega-hydroxylase mediate ciprofibrate-induced PPARalpha-dependent peroxisomal proliferation. J Lipid Res., 48, 924-934 (2007).	0
Karen M Fuenzalida, Mauricio C Aguilera, Daniela G Piderit, Patricio C Ramos, Francisca C Bronfman, Nibaldo C Inestrosa and Miguel Bronfman.	Peroxisome proliferator-activated receptor gamma is a novel target of the nerve growth factor signaling pathway in PC12 cells. J. Biol. Chem. 280, 9604-9609 (2005).	0

Miguel Bronfman

Academic CV

Investigation

Academic CV

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