Tiwari Prafulla Chandra, Pal Rishi
Department of Pharmacology & Therapeutics, King George's Medical University, Utter Pradesh Lucknow-226003, India.
Dialogues Clin Neurosci. 2017 Mar;19(1):71-80. doi: 10.31887/DCNS.2017.19.1/rpal.
Parkinson disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons affected by inflammatory processes. Post-mortem analyses of brain and cerebrospinal fluid from PD patients show the accumulation of proinflammatory cytokines, confirming an ongoing neuroinflammation in the affected brain regions. These inflammatory mediators may activate transcription factors-notably nuclear factor κB, Ying-Yang 1 (YY1), fibroblast growth factor 20 (FGF20), and mammalian target of rapamycin (mTOR)-which then regulate downstream signaling pathways that in turn promote death of dopaminergic neurons through death domain-containing receptors. Dopaminergic neurons are vulnerable to oxidative stress and inflammatory attack. An increased level of inducible nitric oxide synthase observed in the substantia nigra and striatum of PD patients suggests that both cytokine-and chemokine-induced toxicity and inflammation lead to oxidative stress that contributes to degeneration of dopaminergic neurons and to disease progression. Lipopolysaccharide activation of microglia in the proximity of dopaminergic neurons in the substantia nigra causes their degeneration, and this appears to be a selective vulnerability of dopaminergic neurons to inflammation. In this review, we will look at the role of various transcription factors and signaling pathways in the development of PD.
帕金森病（PD）是一种神经退行性疾病，其特征是多巴胺能神经元受到炎症过程的影响。对PD患者的大脑和脑脊液进行的尸检分析显示促炎细胞因子的积累，证实了受影响脑区存在持续的神经炎症。这些炎症介质可能激活转录因子，特别是核因子κB、阴阳1（YY1）、成纤维细胞生长因子20（FGF20）和雷帕霉素哺乳动物靶蛋白（mTOR），然后这些转录因子调节下游信号通路，进而通过含死亡结构域的受体促进多巴胺能神经元的死亡。多巴胺能神经元易受氧化应激和炎症攻击。在PD患者的黑质和纹状体中观察到诱导型一氧化氮合酶水平升高，这表明细胞因子和趋化因子诱导的毒性和炎症都会导致氧化应激，从而导致多巴胺能神经元变性和疾病进展。黑质中多巴胺能神经元附近的小胶质细胞被脂多糖激活会导致其变性，这似乎是多巴胺能神经元对炎症的一种选择性易损性。在这篇综述中，我们将探讨各种转录因子和信号通路在PD发展中的作用。
