Do PPAR-Gamma Agonists Have a Future in Parkinson's Disease Therapy?
Do PPAR-Gamma Agonists Have a Future in Parkinson's Disease Therapy?
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DOI：
10.4061/2011/689181
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Carboni E
中科院分区：
文献类型：
--
作者：
Carta AR;Pisanu A;Carboni E
噻唑烷二酮类(TZD)是一类过氧化物酶体增殖物激活受体(PPAR)-γ激动剂，常用作治疗2型糖尿病的胰岛素增敏药物。在过去的十年中，PPAR-γ激动剂因其在包括帕金森病(PD)在内的多种神经退行性疾病中表现出的神经保护作用而受到越来越多的关注，这可能与这些化合物的抗感染活性有关。最近的研究表明，神经炎症，尤其是反应性小胶质细胞在帕金森病的发病机制中起着重要作用。此外，在PD患者的黑质(SN)中发现了浸润性活化的淋巴细胞后，最近的研究支持了免疫介导的机制在导致慢性神经炎和多巴胺能变性的病理过程中所起的作用。PPAR-γ在中枢和外周免疫系统的细胞中都有高表达，在小胶质细胞激活、单核细胞和T细胞分化中发挥关键作用，是免疫反应的关键调节因子。在这里，我们回顾了PPAR-γ在实验性PD模型中诱导神经保护的临床前证据，并强调了涉及中枢或外周免疫调节活性的相关抗炎机制。直接(中枢)或间接(外周)导致神经炎症的免疫功能的特异性靶向可能代表着PD疾病改善疗法的一种新的治疗方法。
Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor (PPAR)-γ agonists commonly used as insulin-sensitizing drugs for the treatment of type 2 diabetes. In the last decade, PPAR-γ agonists have received increasing attention for their neuroprotective properties displayed in a variety of neurodegenerative diseases, including Parkinson's disease (PD), likely related to the anti-infammatory activity of these compounds. Recent studies indicate that neuroinflammation, specifically reactive microglia, plays important roles in PD pathogenesis. Moreover, after the discovery of infiltrating activated Limphocytes in the substantia nigra (SN) of PD patients, most recent research supports a role of immune-mediated mechanisms in the pathological process leading to chronic neuroinflammation and dopaminergic degeneration. PPAR-γ are highly expressed in cells of both central and peripheral immune systems, playing a pivotal role in microglial activation as well as in monocytes and T cells differentiation, in which they act as key regulators of immune responses. Here, we review preclinical evidences of PPAR-γ-induced neuroprotection in experimental PD models and highlight relative anti-inflammatory mechanisms involving either central or peripheral immunomodulatory activity. Specific targeting of immune functions contributing to neuroinflammation either directly (central) or indirectly (peripheral) may represent a novel therapeutic approach for disease modifying therapies in PD.
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影响因子：
6.1
作者：
Amoruso, Angela;Bardelli, Claudio;Brunelleschi, Sandra
通讯作者：
Brunelleschi, Sandra
DOI：
10.1016/j.bbrc.2009.06.047
发表时间：
2009-08-28
影响因子：
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影响因子：
29
作者：
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通讯作者：
Chinetti-Gbaguidi, Giulia