脑老化和阿尔茨海默病中的小胶质细胞功能障碍。
Microglial dysfunction in brain aging and Alzheimer's disease.
机构信息
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA; Neuroscience IDP Program, Stanford University School of Medicine, Stanford, California 94305, USA.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA; Center for Tissue Regeneration, Repair and Restoration, Veterans Administration Palo Alto Health Care System, Palo Alto, California 94304, USA.
出版信息
Biochem Pharmacol. 2014 Apr 15;88(4):594-604. doi: 10.1016/j.bcp.2014.01.008. Epub 2014 Jan 18.
Microglia, the immune cells of the central nervous system, have long been a subject of study in the Alzheimer's disease (AD) field due to their dramatic responses to the pathophysiology of the disease. With several large-scale genetic studies in the past year implicating microglial molecules in AD, the potential significance of these cells has become more prominent than ever before. As a disease that is tightly linked to aging, it is perhaps not entirely surprising that microglia of the AD brain share some phenotypes with aging microglia. Yet the relative impacts of both conditions on microglia are less frequently considered in concert. Furthermore, microglial "activation" and "neuroinflammation" are commonly analyzed in studies of neurodegeneration but are somewhat ill-defined concepts that in fact encompass multiple cellular processes. In this review, we have enumerated six distinct functions of microglia and discuss the specific effects of both aging and AD. By calling attention to the commonalities of these two states, we hope to inspire new approaches for dissecting microglial mechanisms.
小胶质细胞是中枢神经系统的免疫细胞,由于其对疾病病理生理学的剧烈反应,长期以来一直是阿尔茨海默病(AD)领域的研究对象。由于过去一年的几项大型遗传研究表明小胶质细胞分子与 AD 有关,这些细胞的潜在意义比以往任何时候都更加突出。由于这种疾病与衰老密切相关,AD 大脑中的小胶质细胞与衰老小胶质细胞具有一些表型或许并不完全出人意料。然而,这两种情况对小胶质细胞的相对影响很少被同时考虑。此外,在神经退行性变的研究中,通常会分析小胶质细胞的“激活”和“神经炎症”,但这些概念定义有些模糊,实际上包含多个细胞过程。在这篇综述中,我们列举了小胶质细胞的六种不同功能,并讨论了衰老和 AD 的具体影响。通过关注这两种状态的共同点,我们希望为剖析小胶质细胞机制提供新的方法。