Sprenkle Neil T, Sims Savannah G, Sánchez Cristina L, Meares Gordon P
Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, One Medical Center Drive, BMRC, Morgantown, WV, 311, USA.
Blanchette Rockefeller Neurosciences Institute, West Virginia University School of Medicine, Morgantown, WV, USA.
Mol Neurodegener. 2017 May 25;12(1):42. doi: 10.1186/s13024-017-0183-y.
Persistent endoplasmic reticulum (ER) stress is thought to drive the pathology of many chronic disorders due to its potential to elicit aberrant inflammatory signaling and facilitate cell death. In neurodegenerative diseases, the accumulation of misfolded proteins and concomitant induction of ER stress in neurons contributes to neuronal dysfunction. In addition, ER stress responses induced in the surrounding neuroglia may promote disease progression by coordinating damaging inflammatory responses, which help fuel a neurotoxic milieu. Nevertheless, there still remains a gap in knowledge regarding the cell-specific mechanisms by which ER stress mediates neuroinflammation. In this review, we will discuss recently uncovered inflammatory pathways linked to the ER stress response. Moreover, we will summarize the present literature delineating how ER stress is generated in Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis, and highlight how ER stress and neuroinflammation intersect mechanistically within the central nervous system. The mechanisms by which stress-induced inflammation contributes to the pathogenesis and progression of neurodegenerative diseases remain poorly understood. Further examination of this interplay could present unappreciated insights into the development of neurodegenerative diseases, and reveal new therapeutic targets.
持续性内质网（ER）应激被认为会引发许多慢性疾病的病理过程，因为它有可能引发异常的炎症信号并促进细胞死亡。在神经退行性疾病中，错误折叠蛋白的积累以及神经元中内质网应激的伴随诱导会导致神经元功能障碍。此外，周围神经胶质细胞中诱导的内质网应激反应可能通过协调破坏性的炎症反应来促进疾病进展，而这种炎症反应会助长神经毒性环境。然而，关于内质网应激介导神经炎症的细胞特异性机制，目前仍存在知识空白。在这篇综述中，我们将讨论最近发现的与内质网应激反应相关的炎症途径。此外，我们将总结目前关于阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和多发性硬化症中内质网应激如何产生的文献，并强调内质网应激和神经炎症在中枢神经系统中如何在机制上相互交叉。应激诱导的炎症导致神经退行性疾病发病和进展的机制仍知之甚少。对这种相互作用的进一步研究可能会为神经退行性疾病的发展提供新的见解，并揭示新的治疗靶点。
