Agonism of peroxisome proliferator receptor-gamma may have therapeutic potential for neuroinflammation and Parkinson's disease

Randy L. Hunter, Guoying Bing

Research output: Contribution to journalReview articlepeer-review

50 Scopus citations

Abstract

Evidence suggests inflammation, mitochondria dysfunction, and oxidative stress play major roles in Parkinson's disease (PD), where the primary pathology is the significant loss of dopaminergic neurons in the substantia nigra (SN). Current methods used to treat PD focus mainly on replacing dopamine in the nigrostriatal system. However, with time these methods fail and worsen the symptoms of the disease. This implies there is more to the treatment of PD than just restoring dopamine or the dopaminergic neurons, and that a broader spectrum of factors must be changed in order to restore environmental homeostasis. Pharmacological agents that can protect against progressive neuronal degeneration, increase the level of dopamine in the nigrostriatal system, or restore the dopaminergic system offer various avenues for the treatment of PD. Drugs that reduce inflammation, restore mitochondrial function, or scavenge free radicals have also been shown to offer neuroprotection in various animal models of PD. The activation of peroxisome proliferator receptor-gamma (PPAR-γ) has been associated with altering insulin sensitivity, increasing dopamine, inhibiting inflammation, altering mitochondrial bioenergetics, and reducing oxidative stress - a variety of factors that are altered in PD. Therefore, PPAR-γ activation may offer a new clinically relevant treatment approach to neuroinflammation and PD related neurodegeneration. This review will summarize the current understanding of the role of PPAR-γ agonists in neuroinflammation and discuss their potential for the treatment of PD.

Original languageEnglish
Pages (from-to)35-46
Number of pages12
JournalCurrent Neuropharmacology
Volume5
Issue number1
DOIs
StatePublished - Mar 2007

Keywords

  • Neurodegeneration
  • Neuroinflammation
  • PPAR-gamma
  • Parkinson's disease
  • Pioglitazone

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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