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Repurposing Peroxisome Proliferator-Activated Receptor Agonists in Neurological and Psychiatric Disorders

Claudia Sagheddu1, Miriam Melis1, Anna Lisa Muntoni2

  • 1Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, Italy.

Pharmaceuticals (Basel, Switzerland)
|October 23, 2021
PubMed

Insights

Peroxisome proliferator-activated receptors (PPARs) show neuroprotective potential. Repurposing PPAR-targeting drugs, already safe for metabolic disorders, may offer new treatments for central nervous system diseases.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Convergent pathophysiological mechanisms like oxidative stress, immuno-inflammation, and metabolic dysregulation underlie neurological and neuropsychiatric disorders.
  • Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in regulating anti-inflammatory and neuroprotective genes.
  • Existing PPAR agonists are safe and effective for metabolic and systemic diseases, with some crossing the blood-brain barrier.

Purpose of the Study:

  • To review preclinical and clinical evidence for a neuroprotective role of PPARs.
  • To explore the rationale for repurposing PPAR-targeting drugs for central nervous system (CNS) diseases.

Main Methods:

  • Review of preclinical studies investigating PPARs in CNS conditions.
  • Analysis of clinical trial data for PPAR agonists in neurological and neuropsychiatric diseases.
  • Evaluation of the blood-brain barrier penetration of PPAR-acting drugs.

Main Results:

  • Evidence suggests PPARs exert a neuroprotective effect.
  • PPAR agonists demonstrate potential in counteracting various CNS disorders.
  • Safety and tolerability profiles of PPAR agonists are favorable.

Conclusions:

  • PPARs represent a promising therapeutic target for neurodegenerative and neuropsychiatric conditions.
  • Repurposing established PPAR-targeting drugs offers a viable strategy for CNS disease treatment.
  • Further clinical investigation is warranted to validate PPAR agonists for neurological applications.
Keywords:
N-acylethanolaminesPPARsfenofibratefibratesneuroinflammationpioglitazone

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