Review: PPARs as new therapeutic targets for the treatment of cerebral ischemia/reperfusion injury
Open Access
- 1 June 2008
- journal article
- review article
- Published by SAGE Publications in Therapeutic Advances in Cardiovascular Disease
- Vol. 2 (3), 179-197
- https://doi.org/10.1177/1753944708090924
Abstract
Stroke is a leading cause of death and long-term disability in industrialized countries. Despite advances in understanding its pathophysiology, little progress has been made in the treatment of stroke. The currently available therapies have proven to be highly unsatisfactory (except thrombolysis) and attempts are being made to identify and characterize signaling proteins which could be exploited to design novel therapeutic modalities. The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that control lipid and glucose metabolism. PPARs regulate gene expression by binding with the retinoid X receptor (RXR) as a heterodimeric partner to specific DNA sequences, termed PPAR response elements. In addition, PPARs may modulate gene transcription also by directly interfering with other transcription factor pathways in a DNA-binding independent manner. To date, three different PPAR isoforms, designated α, β/ δ, and γ, have been identified. Recently, they have been found to play an important role for the pathogenesis of various disorders of the central nervous system and accumulating data suggest that PPARs may serve as potential targets for treating ischemic stroke. Activation of all PPAR isoforms, but especially of PPAR γ, was shown to prevent post-ischemic inflammation and neuronal damage in several in vitro and in vivo models, negatively regulating the expression of genes induced by ischemia/ reperfusion (I/R). This paper reviews the evidence and recent developments relating to the potential therapeutic effects of PPAR-agonists in the treatment of cerebral I/R injury.Keywords
This publication has 100 references indexed in Scilit:
- The role of fibrates in the prevention of cardiovascular disease—a pooled meta-analysis of long-term randomized placebo-controlled clinical trialsAmerican Heart Journal, 2007
- PPARs and molecular mechanisms of transrepressionBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2007
- Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial: Design and MethodsThe American Journal of Cardiology, 2007
- The oxidative stress mediator 4-hydroxynonenal is an intracellular agonist of the nuclear receptor peroxisome proliferator-activated receptor-β/δ (PPARβ/δ)Free Radical Biology & Medicine, 2007
- Parallel SUMOylation-Dependent Pathways Mediate Gene- and Signal-Specific Transrepression by LXRs and PPARγMolecular Cell, 2007
- Peroxisome proliferator-activated receptor-γ2 Pro12Ala polymorphism is associated with reduced risk for ischemic stroke with type 2 diabetesNeuroscience Letters, 2006
- Combinatorial roles of nuclear receptors in inflammation and immunityNature Reviews Immunology, 2005
- A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γNature, 2005
- Activation of Human Peroxisome Proliferator-Activated Receptor (PPAR) Subtypes by PioglitazoneBiochemical and Biophysical Research Communications, 2000
- Serum Cholesterol Levels and Six-Year Mortality from Stroke in 350,977 Men Screened for the Multiple Risk Factor Intervention TrialNew England Journal of Medicine, 1989