Department of Pathology, University of Toledo Health Sciences Center, Toledo, OH 43614-2598, USA.
J Alzheimers Dis. 2010;21(1):1-14. doi: 10.3233/JAD-2010-1414.
The concept of neuroinflammation has evolved over the past two decades from an initially controversial viewpoint to its present status as a generally accepted idea whose mechanisms and consequences are still actively under research and debate, particularly with regard to Alzheimer's disease (AD). This review summarizes the current status of neuroinflammation research as it specifically relates to AD. Neuroinflammation is discussed mechanistically with emphasis on the role of redox signal transduction linked to the activation of central nervous system-relevant innate immune pathways. Redox signaling is presented both as a causal factor and a consequence of sustained neuroinflammation. Functional relationships are discussed that connect distinct neuroinflammatory components such as cytokines, eicosanoids, classic AD pathology (amyloid plaques and neurofibrillary tangles), and the recently emergent notion of "damage-associated molecular patterns". The interaction of these paracrine factors likely can produce positive as well as negative effects on the AD brain, ranging from plaque clearance by microglia in the short term to glial dysfunction and neuronal compromise if the neuroinflammation is chronically sustained and unmitigated. Recent disappointments in AD clinical trials of anti-inflammatory drugs are discussed with reference to possible explanations and potential avenues for future pharmacological approaches to the disease.
神经炎症的概念在过去二十年中经历了从最初有争议的观点到目前被广泛接受的观念的演变，其机制和后果仍在积极研究和争论中，特别是在阿尔茨海默病（AD）方面。这篇综述总结了神经炎症研究的现状，特别是与 AD 相关的研究。神经炎症在机制上进行了讨论，重点是与中枢神经系统相关固有免疫途径的激活相关的氧化还原信号转导的作用。氧化还原信号既被认为是持续神经炎症的原因，也是其结果。讨论了将不同的神经炎症成分（如细胞因子、类花生酸、典型的 AD 病理学（淀粉样斑块和神经原纤维缠结）以及最近出现的“损伤相关分子模式”）联系起来的功能关系。这些旁分泌因子的相互作用可能对 AD 大脑产生积极和消极的影响，从短期的小胶质细胞清除斑块到长期持续和无法缓解的神经炎症导致的神经胶质功能障碍和神经元损伤。讨论了 AD 抗炎药物临床试验的近期失败，并参考了可能的解释和未来疾病药物治疗的潜在途径。
