Neuroinflammation in Alzheimer's disease: mechanisms, pathologic consequences, and potential for therapeutic manipulation.
Neuroinflammation in Alzheimer's disease: mechanisms, pathologic consequences, and potential for therapeutic manipulation.
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DOI：
10.3233/jad-2010-1414
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Hensley K
中科院分区：
文献类型：
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作者：
Hensley K
神经炎症的概念在过去的二十年中已经从最初有争议的观点发展到目前普遍接受的观点，其机制和后果仍在积极研究和辩论中，特别是关于阿尔茨海默病（AD）。本文综述了神经炎症研究的现状，因为它特别涉及到AD。神经炎症的机制进行了讨论，重点是与中枢神经系统相关的先天免疫途径的激活氧化还原信号转导的作用。氧化还原信号被认为是持续神经炎症的因果因素和结果。功能的关系进行了讨论，连接不同的神经炎性成分，如细胞因子，类花生酸，经典的AD病理（淀粉样斑块和神经纤维缠结），和最近出现的概念“损伤相关的分子模式”。这些旁分泌因子的相互作用可能会对AD脑产生积极和消极的影响，从短期内小胶质细胞的斑块清除到神经胶质功能障碍和神经元损害（如果神经炎症长期持续且未减轻）。最近在AD的抗炎药物的临床试验的失望进行了讨论，参考可能的解释和潜在的途径，为未来的药理学方法的疾病。
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.