Role of oxidative stress in Parkinson's disease.
Role of oxidative stress in Parkinson's disease.
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DOI：
10.5607/en.2013.22.1.11
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发表时间：
2013-03
影响因子：
2.4
通讯作者：
Hwang O
中科院分区：
文献类型：
--
作者：
Hwang O
帕金森病（Parkinson's disease，PD）是一种进行性神经退行性运动障碍，与黑质背侧部多巴胺（DA）能神经元的选择性丧失和纹状体投射神经纤维的变性有关。由于目前没有延迟神经退行性过程的疗法，因此通过神经保护疗法来改变疾病进程是一个重要的未满足的临床需求。为此，理解使黑质神经元特别脆弱的细胞机制一直是深入研究的主题。越来越多的证据表明氧化应激发挥着重要作用。DA本身的代谢有助于氧化应激，导致细胞内大分子的修饰，这些大分子的功能对细胞存活很重要。线粒体功能障碍和随之而来的活性氧增加也会引发一系列导致细胞死亡的事件。此外，活化的小胶质细胞在神经炎症反应期间产生一氧化氮和超氧化物，并且这被受损的DA能神经元释放的分子如α-突触核蛋白、神经黑色素和基质金属蛋白酶-3加重。因此，减少氧化应激的方法可以提供一种治疗策略。NAD（P）H：醌还原酶（NQO 1）和其他抗氧化酶的基因表达通常受转录因子Nrf 2的调控，可作为开发PD疾病修饰疗法的靶蛋白。
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder associated with a selective loss of the dopamine(DA)rgic neurons in the substantia nigra pars compacta and the degeneration of projecting nerve fibers in the striatum. Because there is currently no therapy that delays the neurodegenerative process, modification of the disease course by neuroprotective therapy is an important unmet clinical need. Toward this end, understanding cellular mechanisms that render the nigral neurons particularly vulnerable have been a subject of intensive research. Increasing evidence suggests that oxidative stress plays a major role. The metabolism of DA itself contributes to oxidative stress, resulting in modification of intracellular macromolecules whose functions are important for cell survival. Mitochondrial dysfunction and the consequent increase in reactive oxygen species also trigger a sequence of events that leads to cell demise. In addition, activated microglia produce nitric oxide and superoxide during neuroinflammatory responses, and this is aggravated by the molecules released by damaged DAergic neurons such as α-synuclein, neuromelanin and matrix metalloproteinase-3. Ways to reduce oxidative stress therefore can provide a therapeutic strategy. NAD(P)H:quinone reductase (NQO1) and other antioxidant enzymes, whose gene expression are commonly under the regulation of the transcription factor Nrf2, can serve as target proteins utilized toward development of disease-modifying therapy for PD.