Department of Molecular and Biomedical Sciences, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.
Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, SA, Australia.
Hum Mol Genet. 2018 Aug 1;27(R2):R108-R118. doi: 10.1093/hmg/ddy139.
The notion that one common pathogenic pathway could account for the various clinically distinguishable, typically late-onset neurodegenerative diseases might appear unlikely given the plethora of diverse primary causes of neurodegeneration. On the contrary, an autoinflammatory pathogenic mechanism allows diverse genetic and environmental factors to converge into a common chain of causality. Inflammation has long been known to correlate with neurodegeneration. Until recently this relationship was seen as one of consequence rather than cause-with inflammatory cells and events acting to 'clean up the mess' after neurological injury. This explanation is demonstrably inadequate and it is now clear that inflammation is at the very least, rate-limiting for neurodegeneration (and more likely, a principal underlying cause in most if not all neurodegenerative diseases), protective in its initial acute phase, but pernicious in its latter chronic phase.
鉴于导致神经退行性病变的各种主要原因纷繁多样，一种普遍的致病途径可以解释各种临床表现明显不同、通常为迟发性神经退行性疾病的观点似乎不太可能成立。相反，自身炎症性致病机制使得各种遗传和环境因素汇聚成一条共同的因果链。炎症与神经退行性病变的相关性早已为人所知。直到最近，这种关系才被视为后果而非原因——炎症细胞和事件在神经损伤后起到“清理混乱”的作用。这种解释显然是不够充分的，现在很明显，炎症至少是神经退行性病变的限速因素（更有可能的是，在大多数（如果不是全部）神经退行性疾病中，它是主要的潜在原因），在其初始急性期具有保护作用，但在后期慢性期则具有危害性。
