Peroxisome proliferator-activated receptor γ (PPARγ)

A master gatekeeper in CNS injury and repair

Wei Cai, Tuo Yang, Huan Liu, Lijuan Han, Kai Zhang, Xiaoming Hu, Xuejing Zhang, Ke Jie Yin, Yanqin Gao, Michael V. L. Bennett, Rehana K. Leak, Jun Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a widely expressed ligand-modulated transcription factor that governs the expression of genes involved in inflammation, redox equilibrium, trophic factor production, insulin sensitivity, and the metabolism of lipids and glucose. Synthetic PPARγ agonists (e.g. thiazolidinediones) are used to treat Type II diabetes and have the potential to limit the risk of developing brain injuries such as stroke by mitigating the influence of comorbidities. If brain injury develops, PPARγ serves as a master gatekeeper of cytoprotective stress responses, improving the chances of cellular survival and recovery of homeostatic equilibrium. In the acute injury phase, PPARγ directly restricts tissue damage by inhibiting the NFκB pathway to mitigate inflammation and stimulating the Nrf2/ARE axis to neutralize oxidative stress. During the chronic phase of acute brain injuries, PPARγ activation in injured cells culminates in the repair of gray and white matter, preservation of the blood-brain barrier, reconstruction of the neurovascular unit, resolution of inflammation, and long-term functional recovery. Thus, PPARγ lies at the apex of cell fate decisions and exerts profound effects on the chronic progression of acute injury conditions. Here, we review the therapeutic potential of PPARγ in stroke and brain trauma and highlight the novel role of PPARγ in long-term tissue repair. We describe its structure and function and identify the genes that it targets. PPARγ regulation of inflammation, metabolism, cell fate (proliferation/differentiation/maturation/survival), and many other processes also has relevance to other neurological diseases. Therefore, PPARγ is an attractive target for therapies against a number of progressive neurological disorders.

Original languageEnglish (US)
JournalProgress in Neurobiology
DOIs
StateAccepted/In press - 2017

Fingerprint

Peroxisome Proliferator-Activated Receptors
Wounds and Injuries
Brain Injuries
Inflammation
Stroke
Thiazolidinediones
Nervous System Diseases
Blood-Brain Barrier
Lipid Metabolism
Type 2 Diabetes Mellitus
Oxidation-Reduction
Insulin Resistance
Comorbidity
Oxidative Stress
Transcription Factors
Cell Proliferation
Ligands
Gene Expression
Glucose

Keywords

  • Inflammation
  • Nrf2
  • Remyelination
  • Stroke
  • Thiazolidinedione
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Peroxisome proliferator-activated receptor γ (PPARγ) : A master gatekeeper in CNS injury and repair. / Cai, Wei; Yang, Tuo; Liu, Huan; Han, Lijuan; Zhang, Kai; Hu, Xiaoming; Zhang, Xuejing; Yin, Ke Jie; Gao, Yanqin; Bennett, Michael V. L.; Leak, Rehana K.; Chen, Jun.

In: Progress in Neurobiology, 2017.

Research output: Contribution to journalArticle

Cai, Wei ; Yang, Tuo ; Liu, Huan ; Han, Lijuan ; Zhang, Kai ; Hu, Xiaoming ; Zhang, Xuejing ; Yin, Ke Jie ; Gao, Yanqin ; Bennett, Michael V. L. ; Leak, Rehana K. ; Chen, Jun. / Peroxisome proliferator-activated receptor γ (PPARγ) : A master gatekeeper in CNS injury and repair. In: Progress in Neurobiology. 2017.
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AB - Peroxisome proliferator-activated receptor γ (PPARγ) is a widely expressed ligand-modulated transcription factor that governs the expression of genes involved in inflammation, redox equilibrium, trophic factor production, insulin sensitivity, and the metabolism of lipids and glucose. Synthetic PPARγ agonists (e.g. thiazolidinediones) are used to treat Type II diabetes and have the potential to limit the risk of developing brain injuries such as stroke by mitigating the influence of comorbidities. If brain injury develops, PPARγ serves as a master gatekeeper of cytoprotective stress responses, improving the chances of cellular survival and recovery of homeostatic equilibrium. In the acute injury phase, PPARγ directly restricts tissue damage by inhibiting the NFκB pathway to mitigate inflammation and stimulating the Nrf2/ARE axis to neutralize oxidative stress. During the chronic phase of acute brain injuries, PPARγ activation in injured cells culminates in the repair of gray and white matter, preservation of the blood-brain barrier, reconstruction of the neurovascular unit, resolution of inflammation, and long-term functional recovery. Thus, PPARγ lies at the apex of cell fate decisions and exerts profound effects on the chronic progression of acute injury conditions. Here, we review the therapeutic potential of PPARγ in stroke and brain trauma and highlight the novel role of PPARγ in long-term tissue repair. We describe its structure and function and identify the genes that it targets. PPARγ regulation of inflammation, metabolism, cell fate (proliferation/differentiation/maturation/survival), and many other processes also has relevance to other neurological diseases. Therefore, PPARγ is an attractive target for therapies against a number of progressive neurological disorders.

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