Fascinatingly, an abundance of recent studies has subscribed to the importance of cytotoxic immune mechanisms that appear to increase the risk/trigger for many progressive neurodegenerative disorders, including Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis, and multiple sclerosis. Events associated with the neuroinflammatory cascades, such as ageing, immunologic dysfunction, and eventually disruption of the blood–brain barrier and the “cytokine storm”, appear to be orchestrated mainly through the activation of microglial cells and communication with the neurons. The inflammatory processes prompt cellular protein dyshomeostasis. Parkinson’s and Alzheimer’s disease share a common feature marked by characteristic pathological hallmarks of abnormal neuronal protein accumulation. These Lewy bodies contain misfolded α-synuclein aggregates in PD or in the case of AD, they are Aβ deposits and tau-containing neurofibrillary tangles. Subsequently, these abnormal protein aggregates further elicit neurotoxic processes and events which contribute to the onset of neurodegeneration and to its progression including aggravation of neuroinflammation. However, there is a caveat for exclusively linking neuroinflammation with neurodegeneration, since it’s highly unlikely that immune dysregulation is the only factor that contributes to the manifestation of many of these neurodegenerative disorders. It is unquestionably a complex interaction with other factors such as genetics, age, and environment. This endorses the “multiple hit hypothesis”. Consequently, if the host has a genetic susceptibility coupled to an age-related weakened immune system, this makes them more susceptible to the virus/bacteria-related infection. This may trigger the onset of chronic cytotoxic neuroinflammatory processes leading to protein dyshomeostasis and accumulation, and finally, these events lead to neuronal destruction. Here, we differentiate “neuroinflammation” and “inflammation” with regard to the involvement of the blood–brain barrier, which seems to be intact in the case of neuroinflammation but defect in the case of inflammation. There is a neuroinflammation-inflammation continuum with regard to virus-induced brain affection. Therefore, we propose a staging of this process, which might be further developed by adding blood- and CSF parameters, their stage-dependent composition and stage-dependent severeness grade. If so, this might be suitable to optimise therapeutic strategies to fight brain neuroinflammation in its beginning and avoid inflammation at all.

令人着迷的是，最近的大量研究都承认细胞毒性免疫机制的重要性，这些机制似乎会增加许多进行性神经退行性疾病的风险/触发因素，包括帕金森病 (PD)、阿尔茨海默病 (AD)、肌萎缩侧索硬化症和多发性硬化症。与神经炎症级联相关的事件，例如衰老、免疫功能障碍以及最终血脑屏障的破坏和“细胞因子风暴”，似乎主要是通过小胶质细胞的激活和与神经元的通讯来精心策划的。炎症过程促使细胞蛋白质稳态失调。帕金森病和阿尔茨海默病有一个​​共同特征，即异常神经元蛋白积累的病理特征。在 PD 中，这些路易体含有错误折叠的 α-突触核蛋白聚集体，在 AD 中，它们是 Aβ 沉积物和含有 tau 蛋白的神经原纤维缠结。随后，这些异常蛋白质聚集体进一步引发神经毒性过程和事件，导致神经变性的发生及其进展，包括神经炎症的加重。然而，需要注意的是，将神经炎症与神经退行性疾病专门联系起来，因为免疫失调不太可能是导致许多神经退行性疾病表现的唯一因素。毫无疑问，这是与遗传、年龄和环境等其他因素的复杂相互作用。这证实了“多重打击假说”。因此，如果宿主具有遗传易感性，加上与年龄相关的免疫系统减弱，这会使他们更容易受到病毒/细菌相关的感染。这可能会引发慢性细胞毒性神经炎症过程，导致蛋白质稳态失调和积累，最后，这些事件导致神经元破坏。在这里，我们根据血脑屏障的参与来区分“神经炎症”和“炎症”，在神经炎症的情况下，血脑屏障似乎是完整的，但在炎症的情况下，血脑屏障似乎是有缺陷的。病毒引起的脑部感染存在神经炎症-炎症连续体。因此，我们建议对该过程进行分期，可以通过添加血液和脑脊液参数、其阶段相关的组成和阶段相关的严重程度来进一步开发。如果是这样，这可能适合优化治疗策略，从一开始就对抗脑神经炎症并完全避免炎症。