University of Bonn, Department of Neurology, Clinical Neurosciences Unit, Bonn, Germany.
Curr Neuropharmacol. 2011 Dec;9(4):643-50. doi: 10.2174/157015911798376325.
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 β-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 PPARγ. This led to the hypothesis that NSAID protection in AD may be partly mediated by PPARγ. Several lines of evidence have supported this hypothesis, using AD related transgenic cellular and animal models. Stimulation of PPARγ 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 PPARγ agonists, therefore PPARγ represents an attractive therapeutic target for the treatment of AD.
过氧化物酶体增殖物激活受体（PPARs）因其在外周代谢中的作用而得到广泛研究，但它们也可能参与各种中枢神经系统（CNS）疾病的发病机制，包括多发性硬化症、肌萎缩侧索硬化症、阿尔茨海默病和帕金森病。观察到 PPARs 能够抑制外周巨噬细胞中的炎症反应，并且在几种人类自身免疫疾病模型中，导致 PPARs 可能对具有炎症成分的 CNS 疾病有益的想法。阿尔茨海默病（AD）过程中的神经炎症反应是由β-淀粉样肽在细胞外斑块中的沉积和持续的神经退行性变引发的。非甾体抗炎药（NSAIDs）被认为可以延迟发病并降低患 AD 的风险，而它们也直接激活 PPARγ。这导致了 NSAID 在 AD 中的保护作用可能部分由 PPARγ介导的假设。使用 AD 相关的转基因细胞和动物模型，有几条证据支持了这一假设。合成激动剂（噻唑烷二酮）刺激 PPARγ 可诱导抗炎、抗淀粉样蛋白和胰岛素增敏作用，这可能解释了观察到的作用。几项临床试验已经使用 PPARγ 激动剂显示出有希望的结果，因此 PPARγ 是治疗 AD 的有吸引力的治疗靶点。
