Review Article Role of PPAR in the Differentiation and Function of Neurons Rodrigo A. Quintanilla, 1,2 Elias Utreras, 3 and Fabián A. Cabezas-Opazo 1 1 Centro de Investigaci´ on Biom´ edica, Universidad Aut´ onoma de Chile, Carlos Ant´ unez 1920, 750056 Santiago, Chile 2 Laboratorio de Neurociencias, Departamento de Neurolog´ ıa, Escuela de Medicina, Pontificia Universidad Cat´ olica de Chile, 8330024 Santiago, Chile 3 Laboratorio de Din´ amica Celular y Neuronal, Departamento de Biolog´ ıa, Facultad de Ciencias, Universidad de Chile, ˜ Nu˜ noa, 7800003 Santiago, Chile Correspondence should be addressed to Rodrigo A. Quintanilla; rodrigo.quintanilla@uautonoma.cl Received 22 May 2014; Revised 31 July 2014; Accepted 16 August 2014; Published 26 August 2014 Academic Editor: Paul D. Drew Copyright © 2014 Rodrigo A. Quintanilla et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Neuronal processes (neurites and axons) have an important role in brain cells communication and, generally, they are damaged in neurodegenerative diseases. Recent evidence has showed that the activation of PPAR pathway promoted neuronal differentiation and axon polarity. In addition, activation of PPAR using thiazolidinediones (TZDs) prevented neurodegeneration by reducing neuronal death, improving mitochondrial function, and decreasing neuroinflammation in neuropathic pain. In this review, we will discuss important evidence that supports a possible role of PPAR in neuronal development, improvement of neuronal health, and pain signaling. erefore, activation of PPAR is a potential target with therapeutic applications against neurodegenerative disorders, brain injury, and pain regulation. 1. Introduction 1.1. Peroxisome Proliferator Activated Receptors. Peroxisome proliferator activated receptors (PPARs) are nuclear receptors that induce signaling and transcription of different pathways [1]. Generally, they participate in the regulation of lipids metabolism and glucose homeostasis, and they also are acti- vated by specific ligands [1–3]. e family of PPARs is mostly composed of three known isoforms: PPAR, PPAR/, and PPAR. ese receptors share a structural homology that consists of four functional units (A, B, C, and D) [1–3]. Unit A/B, located in N-terminal region of the receptor, controls the activation domain by AF-1 ligand, and Units C and D present a DNA binding domain that includes two zinc fingers motives and a docking domain [1–3]. e C-terminal region contains a specific binding domain and a transactivation domain for AF-2 [2]. is region is very important for nuclear localization of the PPARs and other interactions with activator proteins [1–3]. e binding of specific agonists activates the PPARs response, forming a heterodimer complex between PPARs and retinoic acid receptor (RXR), and then this complex will bind to specific PPRE regions in the DNA to activate different target genes [4]. In addition, this dimer can interact with other coactivators proteins like CBP/p300, SRC1, PBP, and PGC-1 to induce a specific gene expression (Figure 1)[3, 4]. PPAR expression is abundant in liver, kidney, and heart and commonly is present in tissues with high metabolic rate [1, 4]. PPAR is activated by polyunsaturated fatty acids, like docosahexaenoic acid (DHA) and icosapentaenoic acid (EPA), and by fibrate drugs like gemfibrozil and fenofibrate, which are currently used as a treatment for dyslipidemia, metabolic syndrome, and cardiovascular damage [1, 3, 4]. PPAR expression is ubiquitous and their abundance depends on the tissue [5]. To this date, evidence suggests that PPAR is activated like PPAR and apparently plays a role in embryo development [5]. PPAR is expressed principally in fatty and vascular tissue [6, 7]; however, it has showed their presence in heart and brain tissue, where their activation reduced cardiovascular damage and neurodegeneration [6, 7]. PPAR is activated by natural ligands like linoleic acid (9- and 13-HODE) and Hindawi Publishing Corporation PPAR Research Volume 2014, Article ID 768594, 9 pages http://dx.doi.org/10.1155/2014/768594