Department of Neuroscience, Health Science Institute, Dokuz Eylul University, Inciralti, 35340 Izmir, Turkey.
Parkinsons Dis. 2011 Feb 22;2011:314082. doi: 10.4061/2011/314082.
Mitochondrial dysfunction is a prominent feature of various neurodegenerative diseases as strict regulation of integrated mitochondrial functions is essential for neuronal signaling, plasticity, and transmitter release. Many lines of evidence suggest that mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson's disease (PD). Several PD-associated genes interface with mitochondrial dynamics regulating the structure and function of the mitochondrial network. Mitochondrial dysfunction can induce neuron death through a plethora of mechanisms. Both mitochondrial dysfunction and neuroinflammation, a common denominator of PD, lead to an increased production of reactive oxygen species, which are detrimental to neurons. The transcription factor nuclear factor E2-related factor 2 (Nrf2, NFE2L2) is an emerging target to counteract mitochondrial dysfunction and its consequences in PD. Nrf2 activates the antioxidant response element (ARE) pathway, including a battery of cytoprotective genes such as antioxidants and anti-inflammatory genes and several transcription factors involved in mitochondrial biogenesis. Here, the current knowledge about the role of mitochondrial dysfunction in PD, Nrf2/ARE stress-response mechanisms, and the evidence for specific links between this pathway and PD are summarized. The neuroprotection of nigral dopaminergic neurons by the activation of Nrf2 through several inducers in PD is also emphasized as a promising therapeutic approach.
线粒体功能障碍是各种神经退行性疾病的一个突出特征，因为整合的线粒体功能的严格调节对于神经元信号转导、可塑性和递质释放至关重要。有许多证据表明，线粒体功能障碍在帕金森病 (PD) 的发病机制中起核心作用。一些与 PD 相关的基因与调节线粒体网络结构和功能的线粒体动力学相互作用。线粒体功能障碍可以通过多种机制诱导神经元死亡。线粒体功能障碍和神经炎症（PD 的共同特征）都会导致活性氧的产生增加，从而对神经元造成损害。转录因子核因子 E2 相关因子 2 (Nrf2，NFE2L2) 是对抗 PD 中线粒体功能障碍及其后果的新兴靶点。Nrf2 激活抗氧化反应元件 (ARE) 途径，包括一系列细胞保护基因，如抗氧化剂和抗炎基因，以及几个参与线粒体生物发生的转录因子。本文总结了线粒体功能障碍在 PD 中的作用、Nrf2/ARE 应激反应机制以及该途径与 PD 之间特定联系的证据。还强调了通过几种 PD 诱导剂激活 Nrf2 对黑质多巴胺能神经元的神经保护作用，这是一种很有前途的治疗方法。
