Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) and Neurodegenerative Disorders
Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) and Neurodegenerative Disorders
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DOI：
10.1007/s12035-012-8259-8
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发表时间：
2012-08-01
影响因子：
5.1
通讯作者：
Lin, Teng-Nan
中科院分区：
文献类型：
--
作者：
Chen, Yu-Chang;Wu, Jui-Sheng;Lin, Teng-Nan
随着全球老龄化人口的持续加速增长，包括阿尔茨海默病（AD）、帕金森病（PD）和中风在内的神经退行性疾病的患病率增加已经引起了公众的极大关注。不幸的是，尽管发现了这些疾病的共同因素，但很少有药物可有效治疗这些疾病。过氧化物酶体增殖物激活受体γ（PPAR-gamma）是一种配体激活的转录因子，属于核激素受体超家族。PPAR-gamma已显示影响多种信号传导网络中大量基因的表达或活性，包括调节胰岛素敏感性、葡萄糖稳态、脂肪酸氧化、免疫应答、氧化还原平衡、心血管完整性和细胞命运。最近的流行病学、临床前动物和临床研究也表明，PPAR-gamma激动剂可以降低许多神经系统疾病的发生率，尽管这些疾病的发展涉及多种病因学因素。在这篇手稿中，我们回顾了目前的知识的机制，潜在的有益效果的PPAR-gamma在不同的神经退行性疾病，特别是，AD，PD和中风，并试图分析这些疾病之间的共同和重叠的功能。我们的研究揭示了PPAR-gamma在多个位点抑制NF-κ B介导的炎症信号传导的能力，并得出结论，PPAR-gamma激动剂代表了一类新的治疗神经炎性疾病的药物。
As the growth of the aging population continues to accelerate globally, increased prevalence of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke, has generated substantial public concern. Unfortunately, despite of discoveries of common factors underlying these diseases, few drugs are available to effectively treat these diseases. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand-activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. PPAR-gamma has been shown to influence the expression or activity of a large number of genes in a variety of signaling networks, including regulation of insulin sensitivity, glucose homeostasis, fatty acid oxidation, immune responses, redox balance, cardiovascular integrity, and cell fates. Recent epidemiological, preclinical animal, and clinical studies also show that PPAR-gamma agonists can lower the incidence of a number of neurological disorders, despite of multiple etiological factors involved in the development of these disorders. In this manuscript, we review current knowledge on mechanisms underlying the beneficial effect of PPAR-gamma in different neurodegenerative diseases, in particular, AD, PD, and stroke, and attempt to analyze common and overlapping features among these diseases. Our investigation unveiled information suggesting the ability for PPAR-gamma to inhibit NF-kappa B-mediated inflammatory signaling at multiple sites, and conclude that PPAR-gamma agonists represent a novel class of drugs for treating neuroinflammatory diseases.