Department of Neurology, Emory University , Atlanta, Georgia .
Antioxid Redox Signal. 2014 Aug 1;21(4):649-67. doi: 10.1089/ars.2014.5859. Epub 2014 Apr 28.
Parkinson's disease (PD) is no longer considered merely a movement disorder caused by degeneration of dopamine neurons in the midbrain. It is now recognized as a widespread neuropathological syndrome accompanied by a variety of motor and nonmotor clinical symptoms. As such, any hypothesis concerning PD pathogenesis and pathophysiology must account for the entire spectrum of disease and not solely focus on the dopamine system.
Based on its anatomy and the intrinsic properties of its neurons, the dorsal motor nucleus of the vagus nerve (DMV) is uniquely vulnerable to damage from PD. Fibers in the vagus nerve course throughout the gastrointestinal (GI) tract to and from the brainstem forming a close link between the peripheral and central nervous systems and a point of proximal contact between the environment and areas where PD pathology is believed to start. In addition, DMV neurons are under high levels of oxidative stress due to their high level of α-synuclein expression, fragile axons, and specific neuronal physiology. Moreover, several consequences of DMV damage, namely, GI dysfunction and unrestrained inflammation, may propagate a vicious cycle of injury affecting vulnerable brain regions.
Current evidence to suggest the vagal system plays a pivotal role in PD pathogenesis is circumstantial, but given the current state of the field, the time is ripe to obtain direct experimental evidence to better delineate it.
Better understanding of the DMV and vagus nerve may provide insight into PD pathogenesis and a neural highway with direct brain access that could be harnessed for novel therapeutic interventions.
帕金森病（PD）不再被认为仅仅是一种由中脑多巴胺神经元退化引起的运动障碍。现在，它被认为是一种广泛的神经病理学综合征，伴有各种运动和非运动临床症状。因此，任何关于 PD 发病机制和病理生理学的假说都必须考虑到疾病的整个谱，而不仅仅是专注于多巴胺系统。
根据其解剖结构和神经元的固有特性，迷走神经背核（DMV）极易受到 PD 的损害。迷走神经纤维贯穿整个胃肠道（GI），往返于脑干，形成外周和中枢神经系统之间的紧密联系，以及 PD 病理学被认为开始的区域与环境之间的近端接触点。此外，由于 DMV 神经元高水平表达α-突触核蛋白、脆弱的轴突和特定的神经元生理学，它们处于高水平的氧化应激下。此外，DMV 损伤的几个后果，即胃肠道功能障碍和不受控制的炎症，可能会引发影响脆弱大脑区域的恶性循环损伤。
目前有证据表明迷走神经系统在 PD 发病机制中起着关键作用，但考虑到该领域的现状，现在是获得直接实验证据以更好地阐明这一问题的时候了。
对 DMV 和迷走神经的更好理解可能为 PD 的发病机制提供深入的了解，并为直接进入大脑的神经高速公路提供可能用于新的治疗干预的途径。
