Peroxisome proliferator-activated receptor gamma: a novel therapeutic target for cognitive impairment and mood disorders that functions via the regulation of adult neurogenesis

Arch Pharm Res. 2021 Jun;44(6):553-563. doi: 10.1007/s12272-021-01333-7. Epub 2021 Jun 17.

Abstract

The proliferation, differentiation, and migration of neural precursor cells occur not only during embryonic development but also within distinct regions of the adult brain through the process of adult neurogenesis. As neurogenesis can potentially regulate brain cognition and neuronal plasticity, the factors that enhance neurogenesis can be attractive therapeutic targets for improving cognitive function and regulating neurodegenerative and neuropsychiatric disorders, including affective and mood disorders. Peroxisome proliferator-activated receptors (PPARs) are a class of ligand-activated transcription factors belonging to the nuclear receptor superfamily. PPARγ is a target for insulin sensitizers and plays an essential role in regulating various metabolic processes, including adipogenesis and glucose homeostasis. Interestingly, evidence demonstrates the role of PPARγ activation in regulating neurogenesis. The pharmacological activation of PPARγ using specific ligands increases the proliferation and differentiation of neural stem cells in specific brain regions, including the hippocampus, and prevents neurodegeneration and improves cognition and anxiety/depression-like behaviors in animal models. We summarize here recent reports on the role of PPARγ in adult neurogenesis, as well as the mechanisms involved, and suggest that PPARγ can serve as a potential therapeutic target for neurological and/or neurodegenerative diseases.

Keywords: Adult neurogenesis; Hippocampus; Nuclear receptor; Peroxisome proliferator-activated receptor.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / metabolism*
  • Cognitive Dysfunction / psychology
  • Drug Delivery Systems / methods
  • Drug Delivery Systems / trends*
  • Humans
  • Mood Disorders / drug therapy
  • Mood Disorders / metabolism*
  • Mood Disorders / psychology
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism*
  • Neurogenesis / drug effects
  • Neurogenesis / physiology*
  • Nootropic Agents / administration & dosage
  • Nootropic Agents / metabolism
  • PPAR gamma / metabolism*

Substances

  • Nootropic Agents
  • PPAR gamma