Department of Neurology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Marcoleta, Santiago, Chile.
J Neurochem. 2010 Mar;112(5):1099-114. doi: 10.1111/j.1471-4159.2009.06537.x. Epub 2009 Dec 10.
Among multiple structural and functional brain changes, aging is accompanied by an increase of inflammatory signaling in the nervous system as well as a dysfunction of the immune system elsewhere. Although the long-held view that aging involves neurocognitive impairment is now dismissed, aging is a major risk factor for neurodegenerative diseases such as Alzheimer;s disease, Parkinson;s disease and Huntington's disease, among others. There are many age-related changes affecting the brain, contributing both to certain declining in function and increased frailty, which could singly and collectively affect neuronal viability and vulnerability. Among those changes, both inflammatory responses in aged brains and the altered regulation of toll like receptors, which appears to be relevant for understanding susceptibility to neurodegenerative processes, are linked to pathogenic mechanisms of several diseases. Here, we review how aging and pro-inflammatory environment could modulate microglial phenotype and its reactivity and contribute to the genesis of neurodegenerative processes. Data support our idea that age-related microglial cell changes, by inducing cytotoxicity in contrast to neuroprotection, could contribute to the onset of neurodegenerative changes. This view can have important implications for the development of new therapeutic approaches.
在多种结构和功能的大脑变化中，衰老伴随着神经系统中炎症信号的增加以及其他地方免疫系统的功能障碍。尽管长期以来人们认为衰老涉及神经认知障碍的观点现在已经被否定，但衰老是阿尔茨海默病、帕金森病和亨廷顿病等神经退行性疾病的主要危险因素。有许多与年龄相关的变化影响大脑，导致某些功能下降和脆弱性增加，这些变化单独或共同影响神经元的存活和易感性。在这些变化中，衰老大脑中的炎症反应以及 Toll 样受体的调节改变，似乎与理解对神经退行性过程的易感性有关，与几种疾病的发病机制有关。在这里，我们回顾了衰老和促炎环境如何调节小胶质细胞表型及其反应性，并有助于神经退行性过程的发生。有数据支持我们的观点，即与神经保护相反，与年龄相关的小胶质细胞变化通过诱导细胞毒性可能有助于神经退行性变化的发生。这种观点对于开发新的治疗方法具有重要意义。
