NADPH oxidases in Parkinson's disease: a systematic review.
NADPH oxidases in Parkinson's disease: a systematic review.
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DOI：
10.1186/s13024-017-0225-5
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发表时间：
2017-11-13
影响因子：
15.1
通讯作者：
Chartier-Harlin MC
中科院分区：
文献类型：
--
作者：
Belarbi K;Cuvelier E;Destée A;Gressier B;Chartier-Harlin MC
帕金森病（PD）是一种进行性运动神经退行性疾病，与脑黑质中多巴胺能神经元的损失相关。氧化应激是一种由于氧化剂和抗氧化剂状态失衡而发生的状况，被认为在多巴胺能神经毒性中起重要作用。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶是多亚基酶复合物，其产生活性氧作为其主要功能。据报道，PD患者脑中NADPH氧化酶催化亚基Nox 1、Nox 2和Nox 4的免疫反应性增加。此外，NADPH氧化酶的敲除或遗传失活发挥神经保护作用，并减少疾病实验模型中病理学的有害方面。然而，NADPH氧化酶和被认为有助于神经元死亡的生物过程之间的联系并不为人所知。本文就NADPH氧化酶在神经元、小胶质细胞和星形胶质细胞中的表达、生理功能及其在帕金森病中的病理生理作用作一综述。它总结了支持小胶质细胞和神经元NADPH氧化酶在与PD相关的细胞紊乱中的作用的发现，如神经炎症、α-突触核蛋白蓄积、线粒体和突触功能障碍或自噬-溶酶体系统的破坏。此外，这篇综述强调了NADPH氧化酶的酶活性所必需的不同步骤，并指出了开发有效的NADPH氧化酶抑制剂治疗PD所要克服的主要障碍。
Parkinson’s disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, is thought to play an important role in dopaminergic neurotoxicity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are multi-subunit enzymatic complexes that generate reactive oxygen species as their primary function. Increased immunoreactivities for the NADPH oxidases catalytic subunits Nox1, Nox2 and Nox4 have been reported in the brain of PD patients. Furthermore, knockout or genetic inactivation of NADPH oxidases exert a neuroprotective effect and reduce detrimental aspects of pathology in experimental models of the disease. However, the connections between NADPH oxidases and the biological processes believed to contribute to neuronal death are not well known. This review provides a comprehensive summary of our current understanding about expression and physiological function of NADPH oxidases in neurons, microglia and astrocytes and their pathophysiological roles in PD. It summarizes the findings supporting the role of both microglial and neuronal NADPH oxidases in cellular disturbances associated with PD such as neuroinflammation, alpha-synuclein accumulation, mitochondrial and synaptic dysfunction or disruption of the autophagy-lysosome system. Furthermore, this review highlights different steps that are essential for NADPH oxidases enzymatic activity and pinpoints major obstacles to overcome for the development of effective NADPH oxidases inhibitors for PD.
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