How to reprogram microglia toward beneficial functions.
How to reprogram microglia toward beneficial functions.
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作者：
Fumagalli M;Lombardi M;Gressens P;Verderio C
小胶质细胞，非神经源性的脑细胞，协调炎症反应的各种侮辱，包括缺氧/缺血或母亲/胎儿感染围产期的大脑。实验研究已经证明了小胶质细胞识别病原体或受损细胞的能力，从而激活可加剧脑损伤的细胞毒性反应。然而，小胶质细胞在其对损伤的反应中显示出巨大的可塑性，并且还可以促进炎症和组织再生的消退阶段。尽管小胶质细胞在脑病理学中的关键作用，但控制小胶质细胞不同表型的细胞机制才刚刚开始被定义。在这里，我们回顾了新兴的策略，以推动小胶质细胞的有益功能，选择性地报告的研究，提供深入的分子机制的表型开关。已经提出了多种方法，其依赖于用药理学试剂、细胞因子、脂质信使或microRNA治疗小胶质细胞，以及依赖于用免疫调节细胞的营养方法或疗法。对小胶质细胞向促再生功能重编程相关的分子机制的分析指出，能量代谢在塑造小胶质细胞功能中起着核心作用。因此，代谢途径的操纵可能提供新的治疗机会，以防止炎症性小胶质细胞的有害作用，并控制大脑疾病中的过度炎症。
Microglia, brain cells of nonneural origin, orchestrate the inflammatory response to diverse insults, including hypoxia/ischemia or maternal/fetal infection in the perinatal brain. Experimental studies have demonstrated the capacity of microglia to recognize pathogens or damaged cells activating a cytotoxic response that can exacerbate brain damage. However, microglia display an enormous plasticity in their responses to injury and may also promote resolution stages of inflammation and tissue regeneration. Despite the critical role of microglia in brain pathologies, the cellular mechanisms that govern the diverse phenotypes of microglia are just beginning to be defined. Here we review emerging strategies to drive microglia toward beneficial functions, selectively reporting the studies which provide insights into molecular mechanisms underlying the phenotypic switch. A variety of approaches have been proposed which rely on microglia treatment with pharmacological agents, cytokines, lipid messengers, or microRNAs, as well on nutritional approaches or therapies with immunomodulatory cells. Analysis of the molecular mechanisms relevant for microglia reprogramming toward pro‐regenerative functions points to a central role of energy metabolism in shaping microglial functions. Manipulation of metabolic pathways may thus provide new therapeutic opportunities to prevent the deleterious effects of inflammatory microglia and to control excessive inflammation in brain disorders.
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影响因子：
7.3
作者：
Amici SA;Dong J;Guerau-de-Arellano M
通讯作者：
Guerau-de-Arellano M
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DOI：
10.1038/mtna.2016.71
发表时间：
2016-09-27
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1202496
发表时间：
2013-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Banerjee S;Xie N;Cui H;Tan Z;Yang S;Icyuz M;Abraham E;Liu G
通讯作者：
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影响因子：
4.6
作者：
Chu B;Wu T;Miao L;Mei Y;Wu M
通讯作者：
Wu M
影响因子：
5.3
作者：
Bouhy, Delphine;Ghasemlou, Nader;David, Samuel
通讯作者：
David, Samuel