Pittsburgh Institute for Neurodegenerative Diseases, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Pittsburgh Institute for Neurodegenerative Diseases, Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Free Radic Biol Med. 2013 Sep;62:111-120. doi: 10.1016/j.freeradbiomed.2013.01.003. Epub 2013 Jan 15.
Parkinson disease (PD), the most common neurodegenerative movement disorder, is associated with selective degeneration of nigrostriatal dopamine neurons. Although the underlying mechanisms contributing to neurodegeneration in PD seem to be multifactorial, mitochondrial impairment and oxidative stress are widely considered to be central to many forms of the disease. Whether oxidative stress is a cause or a consequence of dopaminergic death, there is substantial evidence for oxidative stress both in human PD patients and in animal models of PD, especially using rotenone, a complex I inhibitor. There are many indices of oxidative stress, but this review covers the recent evidence for oxidative damage to nucleic acids, lipids, and proteins in both the brain and the peripheral tissues in human PD and in the rotenone model. Limitations of the existing literature and future perspectives are discussed. Understanding how each particular macromolecule is damaged by oxidative stress and the interplay of secondary damage to other biomolecules may help us design better targets for the treatment of PD.
帕金森病（PD）是最常见的神经退行性运动障碍，与黑质纹状体多巴胺神经元的选择性退化有关。虽然导致 PD 神经退行性变的潜在机制似乎是多因素的，但线粒体损伤和氧化应激被广泛认为是许多形式疾病的核心。无论氧化应激是多巴胺能神经元死亡的原因还是结果，在人类 PD 患者和 PD 动物模型中，特别是使用鱼藤酮（一种复合体 I 抑制剂）时，都有大量氧化应激的证据。有许多氧化应激的指标，但本综述涵盖了在人类 PD 和鱼藤酮模型中，大脑和外周组织中的核酸、脂质和蛋白质的氧化损伤的最新证据。讨论了现有文献的局限性和未来的展望。了解每种特定的大分子如何被氧化应激损伤，以及对其他生物分子的继发性损伤的相互作用，可能有助于我们设计更好的 PD 治疗靶点。
