Esposito Ennio, Di Matteo Vincenzo, Benigno Arcangelo, Pierucci Massimo, Crescimanno Giuseppe, Di Giovanni Giuseppe
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), Italy.
Exp Neurol. 2007 Jun;205(2):295-312. doi: 10.1016/j.expneurol.2007.02.008. Epub 2007 Feb 23.
Parkinson's disease (PD) is known to be a chronic and progressive neurodegenerative disease caused by a selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). A large body of experimental evidence indicates that the factors involved in the pathogenesis of this disease are several, occurring inside and outside the DAergic neuron. Recently, the role of the neuron-glia interaction and the inflammatory process, in particular, has been the object of intense study by the research community. It seems to represent a new therapeutic approach opportunity for this neurological disorder. Indeed, it has been demonstrated that the cyclooxygenase type 2 (COX-2) is up-regulated in SNc DAergic neurons in both PD patients and animal models of PD and, furthermore, non-steroidal anti-inflammatory drugs (NSAIDs) pre-treatment protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6 hydroxydopamine (6-OHDA)-induced nigro-striatal dopamine degeneration. Moreover, recent epidemiological studies have revealed that the risk of developing PD is reduced in humans who make therapeutical use of NSAIDs. Consequently, it is hypothesized that they might delay or prevent the onset of PD. However, whether or not these common drugs may also be of benefit to those individuals who already have Parkinson's disease has not as yet been shown. In this paper, evidence relating to the protective effects of aspirin or other NSAIDs on DAergic neurons in animal models of Parkinson's disease will be discussed. In addition, the pharmacological mechanisms by which these molecules can exert their neuroprotective effects will be reviewed. Finally, epidemiological data exploring the effectiveness of NSAIDs in the prevention of PD and their possible use as adjuvants in the therapy of this neurodegenerative disease will also be examined.
帕金森病（PD）是一种慢性进行性神经退行性疾病，由黑质致密部（SNc）中多巴胺能（DAergic）神经元的选择性退化引起。大量实验证据表明，参与该疾病发病机制的因素有多个，发生在多巴胺能神经元内外。最近，神经元与神经胶质细胞的相互作用以及炎症过程的作用尤其成为研究界深入研究的对象。这似乎为这种神经系统疾病提供了一种新的治疗方法机会。事实上，已经证明，在帕金森病患者和帕金森病动物模型的SNc多巴胺能神经元中，环氧合酶2（COX-2）均上调，此外，非甾体抗炎药（NSAIDs）预处理可防止1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）或6-羟基多巴胺（6-OHDA）诱导的黑质纹状体多巴胺退化。此外，最近的流行病学研究表明，治疗性使用NSAIDs的人患帕金森病的风险降低。因此，据推测它们可能会延迟或预防帕金森病的发作。然而，这些常用药物是否对已经患有帕金森病的个体也有益处尚未得到证实。在本文中，将讨论阿司匹林或其他NSAIDs对帕金森病动物模型中多巴胺能神经元的保护作用的相关证据。此外，还将综述这些分子发挥神经保护作用的药理机制。最后，还将研究探索NSAIDs在预防帕金森病方面的有效性及其作为这种神经退行性疾病治疗辅助药物的可能用途的流行病学数据。
