Department of Anatomy and Neuroscience, Western Gateway Building, University College Cork, Cork, Ireland; Cork Neuroscience Centre, University College Cork, Cork, Ireland.
Parkinsonism Relat Disord. 2018 Nov;56:9-15. doi: 10.1016/j.parkreldis.2018.06.025. Epub 2018 Jun 19.
Parkinson's disease is a common neurodegenerative disorder presenting with a variety of motor and non-motor symptoms. The motor symptoms manifest as a result of the progressive degeneration of midbrain dopaminergic neurons. The axons of these neurons project to the striatum as the nigrostriatal pathway, which is a crucial part of the basal ganglia circuitry controlling movement. In addition to the neuronal degeneration, abnormal intraneuronal α-synuclein protein inclusions called Lewy bodies and Lewy neurites increase in number and spread throughout the nervous system as the disease progresses. While the loss of midbrain dopaminergic neurons is well-established as being central to motor symptoms, there is an increasing focus on the timing of nigrostriatal degeneration, with preclinical evidence suggesting that early axonal degeneration may play a key role in the early stages of Parkinson's disease. Here we review recent evidence for early midbrain dopaminergic axonal degeneration in patients with Parkinson's disease, and explore the potential role of α-synuclein accumulation in this process, with a focus on studies in human populations at the imaging, post-mortem, cellular and molecular levels. Finally, we discuss the implications of this for neurotrophic factor therapies for Parkinson's disease.
帕金森病是一种常见的神经退行性疾病，表现出多种运动和非运动症状。运动症状是由于中脑多巴胺能神经元进行性退化引起的。这些神经元的轴突投射到纹状体作为黑质纹状体通路，这是控制运动的基底神经节回路的重要组成部分。除了神经元退化外，称为路易体和路易神经突的异常细胞内α-突触核蛋白包涵体的数量随着疾病的进展而增加并扩散到整个神经系统。虽然中脑多巴胺能神经元的丧失被认为是运动症状的核心，但人们越来越关注黑质纹状体退化的时间，临床前证据表明，早期轴突退化可能在帕金森病的早期阶段发挥关键作用。在这里，我们回顾了帕金森病患者早期中脑多巴胺能轴突退化的最新证据，并探讨了α-突触核蛋白积累在这一过程中的潜在作用，重点是在影像学、尸检、细胞和分子水平上对人类群体的研究。最后，我们讨论了这对帕金森病神经营养因子治疗的影响。
