The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer's disease brain.
The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer's disease brain.
复制标题
小胶质激活表型对阿尔茨海默氏病大脑中神经退行性和再生的分类。
DOI：
10.1007/s00005-012-0181-2
复制
发表时间：
2012-08
影响因子：
3.2
通讯作者：
Ikezu, Tsuneya
中科院分区：
文献类型：
--
作者：
Varnum, Megan M.;Ikezu, Tsuneya
阿尔茨海默病（Alzheimer's disease，AD）是一种以认知功能和记忆形成进行性下降为特征的神经退行性疾病。没有治疗方法可以阻止或逆转其进展。现代研究表明，年龄依赖性神经炎症变化可能在AD的神经发生减少和认知障碍中起重要作用。先天免疫应答的特征在于巨噬细胞的促炎（M1）活化和随后特异性细胞因子、趋化因子和反应性中间体的产生，随后是抗炎信号传导（M2 a）和伤口愈合（M2 c）的消退和替代活化。我们提出，小胶质细胞的活化表型是类似的巨噬细胞，它们的活化在调节大脑中的神经发生中起着重要的作用。小胶质细胞在衰老过程中经历从M2-到M1-偏斜激活表型的转换。这篇综述将评估神经免疫学研究，导致不同的小胶质细胞激活状态的特征，使用AD小鼠模型。它还将讨论小胶质细胞激活在AD神经发生中的作用，并提出抗炎分子作为令人兴奋的研究治疗靶点。白细胞介素-4和CD 200等分子已被证明是调节大脑神经炎症的重要抗炎分子，将详细讨论它们的治疗潜力。
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive decline of cognitive function and memory formation. There is no therapeutic that can halt or reverse its progression. Contemporary research suggests that age-dependent neuroinflammatory changes may play a significant role in the decreased neurogenesis and cognitive impairments in AD. The innate immune response is characterized by pro-inflammatory (M1) activation of macrophages and subsequent production of specific cytokines, chemokines, and reactive intermediates, followed by resolution and alternative activation for anti-inflammatory signaling (M2a) and wound healing (M2c). We propose that microglial activation phenotypes are analogous to those of macrophages and that their activation plays a significant role in regulating neurogenesis in the brain. Microglia undergo a switch from an M2- to an M1-skewed activation phenotype during aging. This review will assess the neuroimmunological studies that led to characterization of the different microglial activation states using AD mouse models. It will also discuss the roles of microglial activation on neurogenesis in AD and propose anti-inflammatory molecules as exciting therapeutic targets for research. Molecules like interleukin-4 and CD200 have proven to be important anti-inflammatory molecules in the regulation of neuroinflammation in the brain, and they will be discussed in detail for their therapeutic potential.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.2
作者：
Benzing, WC;Wujek, JR;Brunden, KR
通讯作者：
Brunden, KR
影响因子：
3.5
作者：
BAUER, J;STRAUSS, S;BERGER, M
通讯作者：
BERGER, M
影响因子：
6
作者：
Broderick, C;Hoek, RM;Dick, AD
通讯作者：
Dick, AD
影响因子：
--
作者：
Aizenstein, Howard Jay;Nebes, Robert D.;Saxton, Judith A.;Price, Julie C.;Mathis, Chester A.;Tsopelas, Nicholas D.;Ziolko, Scott K.;James, Jeffrey A.;Snitz, Beth E.;Houck, Patricia R.;Bi, Wenzhu;Cohen, Ann D.;Lopresti, Brian J.;DeKosky, Steven T.;Halligan, Edythe M.;Klunk, William E.
通讯作者：
Klunk, William E.