Faculty of Medicine, Institute of Neuropathology, University of Freiburg, Freiburg, Germany.
Department of Neuroscience, Section Medical Physiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
CNS Drugs. 2017 Dec;31(12):1057-1082. doi: 10.1007/s40263-017-0483-3.
Over the past few decades, research on Alzheimer's disease (AD) has focused on pathomechanisms linked to two of the major pathological hallmarks of extracellular deposition of beta-amyloid peptides and intra-neuronal formation of neurofibrils. Recently, a third disease component, the neuroinflammatory reaction mediated by cerebral innate immune cells, has entered the spotlight, prompted by findings from genetic, pre-clinical, and clinical studies. Various proteins that arise during neurodegeneration, including beta-amyloid, tau, heat shock proteins, and chromogranin, among others, act as danger-associated molecular patterns, that-upon engagement of pattern recognition receptors-induce inflammatory signaling pathways and ultimately lead to the production and release of immune mediators. These may have beneficial effects but ultimately compromise neuronal function and cause cell death. The current review, assembled by participants of the Chiclana Summer School on Neuroinflammation 2016, provides an overview of our current understanding of AD-related immune processes. We describe the principal cellular and molecular players in inflammation as they pertain to AD, examine modifying factors, and discuss potential future therapeutic targets.
在过去的几十年中，阿尔茨海默病（AD）的研究主要集中在与两种主要病理学特征相关的发病机制上，即细胞外β-淀粉样肽沉积和神经元内神经原纤维形成。最近，由遗传、临床前和临床研究的结果表明，第三种疾病成分，即由脑固有免疫细胞介导的神经炎症反应，已成为研究的焦点。在神经退行性变过程中产生的各种蛋白质，包括β-淀粉样蛋白、tau、热休克蛋白和嗜铬粒蛋白等，作为危险相关分子模式，一旦与模式识别受体结合，就会诱导炎症信号通路，最终导致免疫介质的产生和释放。这些免疫介质可能具有有益的作用，但最终会损害神经元功能并导致细胞死亡。本综述由 2016 年奇克拉纳暑期学校神经炎症课程的参与者编写，概述了我们目前对 AD 相关免疫过程的理解。我们描述了与 AD 相关的炎症的主要细胞和分子参与者，检查了调节因素，并讨论了潜在的未来治疗靶点。
