A changing perspective on the role of neuroinflammation in Alzheimer's disease.
A changing perspective on the role of neuroinflammation in Alzheimer's disease.
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DOI：
10.1155/2012/495243
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发表时间：
2012
影响因子：
--
通讯作者：
Wilcock DM
中科院分区：
文献类型：
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作者：
Wilcock DM
阿尔茨海默病 (AD) 是一种复杂的神经退行性疾病，其特征是大脑中存在淀粉样斑块和神经原纤维缠结。神经胶质细胞，特别是小胶质细胞，对淀粉样斑块和神经原纤维缠结的存在作出反应，产生炎症反应。虽然曾经被认为由于血脑屏障而具有免疫特权，但现在人们了解到大脑的神经胶质细胞能够产生复杂的炎症反应。本文将讨论有关神经炎症在 AD 病理调节中的不同作用的已发表文献。然后，这些数据将与充分表征的巨噬细胞表型相关。结论是大脑的神经胶质细胞能够产生一系列巨噬细胞反应，称为 M1、M2a、M2b 和 M2c。这些状态与 AD 病理之间的关系仍相对未被充分研究，但已发表的使用各种炎症刺激的数据提供了一些见解。看来 M1 型反应会降低淀粉样蛋白负荷，但会加剧神经原纤维缠结病理。相比之下，M2a 伴随着淀粉样蛋白负荷的升高，并且似乎在一定程度上改善了神经原纤维病理学。总体而言，显然需要进行更有针对性的因果研究，以更好地确定每种炎症状态如何调节 AD 的病理。
Alzheimer's disease (AD) is a complex, neurodegenerative disorder characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain. Glial cells, particularly microglial cells, react to the presence of the amyloid plaques and neurofibrillary tangles producing an inflammatory response. While once considered immunologically privileged due to the blood-brain barrier, it is now understood that the glial cells of the brain are capable of complex inflammatory responses. This paper will discuss the published literature regarding the diverse roles of neuroinflammation in the modulation of AD pathologies. These data will then be related to the well-characterized macrophage phenotypes. The conclusion is that the glial cells of the brain are capable of a host of macrophage responses, termed M1, M2a, M2b, and M2c. The relationship between these states and AD pathologies remains relatively understudied, yet published data using various inflammatory stimuli provides some insight. It appears that an M1-type response lowers amyloid load but exacerbates neurofibrillary tangle pathology. In contrast, M2a is accompanied by elevated amyloid load and appears to ameliorate, somewhat, neurofibrillary pathology. Overall, it is clear that more focused, cause-effect studies need to be performed to better establish how each inflammatory state can modulate the pathologies of AD.