Impact and Therapeutic Potential of PPARs in Alzheimer's Disease

来自 NCBI

阅读量：

作者：

MP Kummer，M Hull，E Reyes-Irisarri，MT Heneka

展开

摘要：

Peroxisome proliferator activated receptors (PPARs) are well studied for their role of peripheral metabolism, but they also may be involved in the pathogenesis of various disorders of the central nervous system (CNS) including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's and, Parkinson's disease. The observation that PPARs are able to suppress the inflammatory response in peripheral macrophages and in several models of human autoimmune diseases, lead to the idea that PPARs might be beneficial for CNS disorders possessing an inflammatory component. The neuroinflammatory response during the course of Alzheimer's disease (AD) is triggered by the deposition of the -amyloid peptide in extracellular plaques and ongoing neurodegeneration. Non-steroidal anti-inflammatory drugs (NSAIDs) have been considered to delay the onset and reduce the risk to develop Alzheimer's disease, while they also directly activate PPAR. This led to the hypothesis that NSAID protection in AD may be partly mediated by PPAR. Several lines of evidence have supported this hypothesis, using AD related transgenic cellular and animal models. Stimulation of PPAR by synthetic agonist (thiazolidinediones) inducing anti-inflammatory, anti-amyloidogenic and insulin sensitizing effects may account for the observed effects. Several clinical trials already revealed promising results using PPAR agonists, therefore PPAR represents an attractive therapeutic target for the treatment of AD.

展开

关键词：

Neuroinflammation alzheimer's disease thiazolidinedione PPAR Therapeutic Potential activated receptors (PPARs) Non-steroidal anti-inflammatory drug PPAR activation retinoid-X-receptors (RXRs)

DOI：

10.2174/157015911798376325

被引量：

年份：

2011