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Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) and Neurodegenerative Disorders

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Abstract

As the growth of the aging population continues to accelerate globally, increased prevalence of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke, has generated substantial public concern. Unfortunately, despite of discoveries of common factors underlying these diseases, few drugs are available to effectively treat these diseases. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. PPAR-γ has been shown to influence the expression or activity of a large number of genes in a variety of signaling networks, including regulation of insulin sensitivity, glucose homeostasis, fatty acid oxidation, immune responses, redox balance, cardiovascular integrity, and cell fates. Recent epidemiological, preclinical animal, and clinical studies also show that PPAR-γ agonists can lower the incidence of a number of neurological disorders, despite of multiple etiological factors involved in the development of these disorders. In this manuscript, we review current knowledge on mechanisms underlying the beneficial effect of PPAR-γ in different neurodegenerative diseases, in particular, AD, PD, and stroke, and attempt to analyze common and overlapping features among these diseases. Our investigation unveiled information suggesting the ability for PPAR-γ to inhibit NF-κB-mediated inflammatory signaling at multiple sites, and conclude that PPAR-γ agonists represent a novel class of drugs for treating neuroinflammatory diseases.

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Acknowledgment

This work was supported by grants from National Science Council and Academia Sinica in Taiwan.

The <networks, functional analyses, pathways…etc.> were generated through the use of IPA (Ingenuity Systems, www.ingenuity.com). The set of molecules are the user's dataset or molecules in Ingenuity's Knowledge Base (genes, endogenous chemicals, or both).

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Authors declare no conflict of interest.

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Authors and Affiliations

  1. Neuroscience Division, Institute of Biomedical Sciences, Academia Sinica, Rm 404, Taipei, 11529, Taiwan, Republic of China

    Yu-Chang Chen, Jui-Sheng Wu, Hsin-Da Tsai, Chien-Yu Huang, Jin-Jer Chen & Teng-Nan Lin

  2. Department of Biochemistry, University of Missouri, Columbia, MO, USA

    Grace Y. Sun

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  1. Yu-Chang Chen
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Correspondence to Teng-Nan Lin.

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Chen, YC., Wu, JS., Tsai, HD. et al. Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) and Neurodegenerative Disorders. Mol Neurobiol 46, 114–124 (2012). https://doi.org/10.1007/s12035-012-8259-8

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