Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
Animal Science Department, Plants for Human Health Institute, NC State University, Kannapolis, North Carolina, USA.
Antioxid Redox Signal. 2020 Jul 20;33(3):191-210. doi: 10.1089/ars.2020.8076. Epub 2020 Apr 9.
Accumulating evidence suggests that inflammation is a major contributor in the pathogenesis of several highly prevalent, but also rare, neurological diseases. In particular, the neurodegenerative processes of Alzheimer's disease (AD), vascular dementia (VAD), Parkinson's disease (PD), and multiple sclerosis (MS) are fueled by neuroinflammation, which, in turn, is accompanied by a parallel systemic immune dysregulation. This cross-talk between periphery and the brain becomes substantial when the bloodbrain barrier loses its integrity, as often occurs in the course of these diseases. It has been hypothesized that the perpetual bidirectional flux of inflammatory mediators is not a mere "static" collateral effect of the neurodegeneration, but represents a proactive phenomenon sparking and driving the neuropathological processes. However, the upstream/downstream relationship between inflammatory events and neurological pathology is still unclear. Solid recent evidence clearly suggests that metabolic factors, systemic infections, Microbiota dysbiosis, and oxidative stress are implicated, although to a different extent, in the development in brain diseases. Here, we reviewed the most solid published evidence supporting the implication of the axis systemic inflammationneuroinflammationneurodegeneration in the pathogenesis of AD, VAD, PD, and MS, highlighting the possible cause of the putative downstream component of the axis. Reaching a definitive clinical/epidemiological appreciation of the etiopathogenic significance of the connection between peripheral and brain inflammation in neurologic disorders is pivotal since it could open novel therapeutic avenues for these diseases.
越来越多的证据表明，炎症是几种高发但也罕见的神经疾病发病机制中的主要因素。特别是阿尔茨海默病（AD）、血管性痴呆（VAD）、帕金森病（PD）和多发性硬化症（MS）的神经退行性过程受到神经炎症的推动，而神经炎症反过来又伴随着平行的全身免疫失调。当血脑屏障失去完整性时，这种外周和大脑之间的串扰就会变得很严重，这种情况在这些疾病的发展过程中经常发生。有人假设，炎症介质的持续双向流动不仅仅是神经退行性变的“静态”附带效应，而是代表了引发和驱动神经病理过程的主动现象。然而，炎症事件与神经病理学之间的上下游关系仍不清楚。最近的有力证据清楚地表明，代谢因素、全身感染、微生物失调和氧化应激虽然在不同程度上与大脑疾病的发展有关，但也与大脑疾病的发展有关。在这里，我们回顾了最有力的已发表证据，这些证据支持系统性炎症-神经炎症-神经退行性变轴在 AD、VAD、PD 和 MS 发病机制中的作用，强调了该轴下游成分的可能原因。明确认识到外周和大脑炎症之间的联系在神经紊乱中的发病机制意义至关重要，因为这可能为这些疾病开辟新的治疗途径。
