PPAR agonists as therapeutics for CNS trauma and neurological diseases

Shweta Mandrekar-Colucci, Andrew Sauerbeck, Phillip G. Popovich, Dana M. McTigue

Research output: Contribution to journalReview articlepeer-review

67 Scopus citations

Abstract

Traumatic injury or disease of the spinal cord and brain elicits multiple cellular and biochemical reactions that together cause or are associated with neuropathology. Specifically, injury or disease elicits acute infiltration and activation of immune cells, death of neurons and glia, mitochondrial dysfunction, and the secretion of substrates that inhibit axon regeneration. In some diseases, inflammation is chronic or non-resolving. Ligands that target PPARs (peroxisome proliferator-activated receptors), a group of ligand-activated transcription factors, are promising therapeutics for neurologic disease and CNS injury because their activation affects many, if not all, of these interrelated pathologic mechanisms. PPAR activation can simultaneously weaken or reprogram the immune response, stimulate metabolic and mitochondrial function, promote axon growth and induce progenitor cells to differentiate into myelinating oligodendrocytes. PPAR activation has beneficial effects in many pre-clinical models of neurodegenerative diseases and CNS injury; however, the mechanisms through which PPARs exert these effects have yet to be fully elucidated. In this review we discuss current literature supporting the role of PPAR activation as a therapeutic target for treating traumatic injury and degenerative diseases of the CNS.

Original languageEnglish
Article numbere00129
Pages (from-to)347-362
Number of pages16
JournalASN Neuro
Volume5
Issue number5
DOIs
StatePublished - 2013

Keywords

  • Alzheimer's disease
  • Astrocyte
  • Experimental autoimmune encephalomyelitis (EAE)
  • Macrophage
  • Multiple sclerosis
  • Spinal cord injury

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