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Neuroprotection by dietary restriction and the PPAR transcription complex

  • Review Article
  • Published:
Translational Neuroscience

Abstract

Although the pathophysiology of neurodegenerative diseases is distinct for each disease, considerable evidence suggests that a single manipulation, dietary restriction, is strikingly protective against a wide range of such diseases. Thus pharmacological mimetics of dietary restrictions could prove widely protective across a range of neurodegenerative diseases. The PPAR transcription complex functions to re-program gene expression in response to nutritional deprivation as well as in response to a wide variety of lipophilic compounds. In mammals there are three PPAR homologs, which dimerize with RXR homologs and recruit coactivators Pgc1-alpha and Creb-binding protein (Cbp). PPARs are currently of clinical interest mainly because PPAR activators are approved for use in humans to reduce lipidemia and to improve glucose control in Type 2 diabetic patients. However, pharmacological enhancement of the activity of the PPAR complex is neuroprotective across a wide variety of models for neuropathological processes, including stroke, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Conversely activity of the PPAR transcriptional complex is reduced in a variety of neuropathological processes. The main mechanisms mediating the neuroprotective effects of the PPAR transcription complex appear to be re-routing metabolism away from glucose metabolism and toward alternative subtrates, and reduction in inflammatory processes. Recent evidence suggests that the PPAR transcriptional complex may also mediate protective effects of dietary restriction on neuropathological processes. Thus this complex represents one of the most promising for the development of pharmacological treatment of neurodegenerative diseases.

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Authors and Affiliations

  1. Department of Neurosciences and Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Charles V. Mobbs, Cesar L. Moreno, Esther S. Kim, Nydia Ekasumara & Bridget K. Marcellino

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  1. Charles V. Mobbs
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  2. Cesar L. Moreno
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  3. Esther S. Kim
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  4. Nydia Ekasumara
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  5. Bridget K. Marcellino
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Correspondence to Charles V. Mobbs.

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Mobbs, C.V., Moreno, C.L., Kim, E.S. et al. Neuroprotection by dietary restriction and the PPAR transcription complex. Translat.Neurosci. 3, 234–241 (2012). https://doi.org/10.2478/s13380-012-0035-8

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  • DOI: https://doi.org/10.2478/s13380-012-0035-8

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