Microglia and Aging: The Role of the TREM2-DAP12 and CX3CL1-CX3CR1 Axes.
Microglia and Aging: The Role of the TREM2-DAP12 and CX3CL1-CX3CR1 Axes.
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DOI：
10.3390/ijms19010318
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发表时间：
2018-01-22
影响因子：
5.6
通讯作者：
Arcuri C
中科院分区：
文献类型：
--
作者：
Mecca C;Giambanco I;Donato R;Arcuri C
根据物种的不同，小胶质细胞占成人大脑胶质细胞的5-20%。作为大脑的先天免疫效应器，小胶质细胞参与多种功能：炎症调节、突触连接、程序性细胞死亡、布线和电路形成、细胞碎片吞噬、突触修剪和产后神经回路雕刻。此外，小胶质细胞还会导致一些神经发育障碍，如Nasu-Hakola病（NHD），以及与年龄相关的神经退行性疾病，如阿尔茨海默病（AD）、帕金森病（PD）等。有证据表明，人类和啮齿动物的小胶质细胞可能会衰老。这一事件决定了小胶质细胞激活状态的改变，与慢性炎症表型和神经保护功能的丧失相关，从而导致对衰老的神经退行性疾病的更大易感性。在中枢神经系统（CNS）中，髓系细胞2-DNAX激活蛋白12 （TREM2-DAP12）是一种仅在小胶质细胞中表达的信号复合物。作为一种小胶质表面受体，TREM2与DAP12相互作用，启动信号转导通路，促进小胶质细胞活化、吞噬和小胶质细胞存活。tre2 - dap12功能缺陷在多种疾病的发病机制中发挥核心作用。CX3CL1 (fractalkine)-CX3CR1信号是神经元和小胶质细胞之间最重要的通讯通道。CX3CR1在神经元中的表达及其受体CX3CR1在小胶质细胞中的表达决定了一种特定的相互作用，在这些细胞的成熟和功能调控中起着重要作用。在这里，我们回顾了TREM2-DAP12和CX3CL1-CX3CR1轴在衰老小胶质细胞中的作用，以及这些通路在生理性中枢神经系统衰老和年龄相关神经退行性疾病中的作用。
Depending on the species, microglial cells represent 5–20% of glial cells in the adult brain. As the innate immune effector of the brain, microglia are involved in several functions: regulation of inflammation, synaptic connectivity, programmed cell death, wiring and circuitry formation, phagocytosis of cell debris, and synaptic pruning and sculpting of postnatal neural circuits. Moreover, microglia contribute to some neurodevelopmental disorders such as Nasu-Hakola disease (NHD), and to aged-associated neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and others. There is evidence that human and rodent microglia may become senescent. This event determines alterations in the microglia activation status, associated with a chronic inflammation phenotype and with the loss of neuroprotective functions that lead to a greater susceptibility to the neurodegenerative diseases of aging. In the central nervous system (CNS), Triggering Receptor Expressed on Myeloid Cells 2-DNAX activation protein 12 (TREM2-DAP12) is a signaling complex expressed exclusively in microglia. As a microglial surface receptor, TREM2 interacts with DAP12 to initiate signal transduction pathways that promote microglial cell activation, phagocytosis, and microglial cell survival. Defective TREM2-DAP12 functions play a central role in the pathogenesis of several diseases. The CX3CL1 (fractalkine)-CX3CR1 signaling represents the most important communication channel between neurons and microglia. The expression of CX3CL1 in neurons and of its receptor CX3CR1 in microglia determines a specific interaction, playing fundamental roles in the regulation of the maturation and function of these cells. Here, we review the role of the TREM2-DAP12 and CX3CL1-CX3CR1 axes in aged microglia and the involvement of these pathways in physiological CNS aging and in age-associated neurodegenerative diseases.
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影响因子：
5.3
作者：
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通讯作者：
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