小胶质细胞在阿尔茨海默病发病机制中的作用

doi:10.16352/j.issn.1001-6325.2024.12.1746

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (12): 1746-1750.doi: 10.16352/j.issn.1001-6325.2024.12.1746

小胶质细胞在阿尔茨海默病发病机制中的作用

吕浪漫^*, 陈绍祥

毕节医学高等专科学校基础医学系生理教研室,贵州毕节 551700

收稿日期:2024-03-07 修回日期:2024-06-04 出版日期:2024-12-05 发布日期:2024-11-26
通讯作者: ^*2308466762@qq.com

The role of microglia in the pathogenesis of Azheimer's disease

LYU Langman^*, CHEN Shaoxiang

Teaching and Research Section of Physiology, Department of Basic Medicine, Bijie College of Medicine, Bijie 551700,China

Received:2024-03-07 Revised:2024-06-04 Online:2024-12-05 Published:2024-11-26
Contact: ^*2308466762@qq.com

摘要/Abstract

摘要： 阿尔茨海默病(AD)是最常见的一种神经退行性疾病。小胶质细胞是中枢神经系统中固有的免疫细胞,调控和监测周围内环境的稳定。小胶质细胞被激活后作用有限,可吞噬部分淀粉样蛋白(Aβ),而Aβ增加后会引起过度激活的小胶质细胞诱发慢性神经炎性反应,进而产生神经毒性影响阿尔茨海默病的病程。即小胶质细胞在神经炎性反应中的作用及在AD发病过程中的作用不容忽视,探讨以小胶质细胞为潜在靶点,旨在为AD的发病机制和临床治疗提供新的切入点。

关键词: 阿尔茨海默病, 小胶质细胞, 神经炎性反应, 激活

Abstract: Alzheimer's disease (AD) is the most common neurodegenerative disease. Microglia are inherent immune cells in the central nervous system, regulating and monitoring the stability of the surrounding environment. After activation, microglia have limited effects and can phagocytose part Aβ,However,Aβ Increased levels of microglia can induce chronic neuroinflammatory responses, leading to neurotoxicity and affecting the course of Alzheimer's disease. The role of microglia in neuroinflammatory response and the pathogenesis of Alzheimer's disease can not be ignored. This study aims to explore the potential target of microglia and provide a new entry point for the pathogenesis and clinical treatment of Alzheimer's disease.

Key words: Alzheimer's disease, microglia, neuroinflammation, activation

中图分类号:

R338

吕浪漫, 陈绍祥. 小胶质细胞在阿尔茨海默病发病机制中的作用[J]. 基础医学与临床, 2024, 44(12): 1746-1750.

LYU Langman, CHEN Shaoxiang. The role of microglia in the pathogenesis of Azheimer's disease[J]. Basic & Clinical Medicine, 2024, 44(12): 1746-1750.

参考文献

[1]Bivona G, Iemmolo M, Agnello L, et al. Microglial activation and priming in Alzheimer's disease: state of the art and future perspectives[J]. Int J Mol Sci,2023,24:884.doi: 10.3390/ijms24010884.
[2]Wang C, Zong S, Cui X, et al. The effects of microglia-associated neuroinflammation on Alzheimer's disease[J]. Front Immunol,2023,14:1117172.doi: 10.3389/fimmu.2023.1117172.
[3]Rostagno AA. Pathogenesis of Alzheimer's disease[J]. Int J Mol Sci, 2022, 24:107. doi: 10.3390/ijms24010107.
[4]Wendimu MY,Hooks SB.Microglia phenotypes in aging and neurodegenerative diseases[J]. Cells,2022,11:2091.doi: 10.3390/cells11132091.
[5]Lier J,Streit W J,Bechmann I. Beyond activation:characterizing microglial functional phenotypes[J]. Cells,2021,10:2236.doi: 10.3390/cells10092236.
[6]Wendimu MY, Hooks SB.Microglia phenotypes in aging and neurodegenerative diseases[J].Cells,2022,11:2091.doi: 10.3390/cells11132091.
[7]Li Q,Wu Y,Chen J,et al. Microglia and immunotherapy in Alzheimer's disease[J]. Acta neurologica Scandinavica,2022,145:273-278.
[8]Cai Y, Liu J, Wang B, et al. Microglia in the neuroinflammatory pathogenesis of Alzheimer's disease and related therapeutic targets[J]. Front Immunol,2022,13:856376. doi: 10.3389/fimmu.2022.856376.
[9]Guo S,Wang H,Yin Y. Microglia polarization from M1 to M2 in neurodegenerative diseases[J]. Front Aging Neurosci, 2022,14:815347. doi: 10.3389/fnagi.2022.815347.
[10]Zhang X, Sun D, Zhou X, et al. Proinflammatory S100A9 stimulates TLR4/NF-κB signaling pathways causing enhanced phagocytic capacity of microglial cells[J].Immunol Lett, 2023,255:54-61.
[11]Lan X,Han X,Li Q, et al. Modulators of microglial activation and polarization after intracerebral haemorrhage[J]. Nat Rev Neurol,2017,13:420-433.
[12]He Y,Gao Y,Zhang Q, et al. IL-4 switches microglia/macrophage M1/M2 polarization and alleviates neurological damage by modulating the JAK1/STAT6 pathway following ICH[J]. Neuroscience,2020,437:161-171.
[13]Hou J, Chen Y, Grajales-Reyes G, et al. TREM2 dependent and independent functions of microglia in Alzheimer's disease[J].Mol Neurodegener,2022,17:84.doi: 10.1186/s13024-022-00588-y.
[14]Wang Y,Zhu T,Wang M, et al. Icariin attenuates M1 activation of microglia and Aβ plaque accumulation in the hippocampus and prefrontal cortex by up-regulating PPARγ in restraint/isolation-stressed APP/PS1 mice[J]. Front Neurosci, 2019, 13:291. doi: 10.3389/fnins.2019.00291.
[15]Dabi YT, Ajagbe AO, Degechisa ST. Toll-like receptors in pathogenesis of neurodegenerative diseases and their therapeutic potential[J]. Immun Inflamm Dis,2023,11:e839.doi: 10.1002/iid3.839.
[16]Thakur S, Dhapola R, Sarma P,et al. Neuroinflammation in Alzheimer's disease: current progress in molecular signaling and therapeutics[J].Inflammation,2023,46:1-17.doi: 10.1007/s10753-022-01721-1.
[17]Merighi S, Nigro M, Travagli A, et al. Microglia and Alzheimer's disease[J]. Int J Mol Sci,2022,23:12990.doi: 10.3390/ijms232112990.
[18]吴艺舸, 宋丽娟, 丁智斌等. 代谢因素影响小胶质细胞极化在阿尔茨海默病中的作用及机制[J].中国免疫学杂志, 2024,40:414-420.
[19]Mander BA, Dave A, Lui KK, et al. Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to beta-amyloid positivity[J].Sleep,2022,45:zsac135.doi: 10.1093/sleep/zsac135.
[20]St-Pierre MK, Carrier M, Gonzalez Ibanez F, et al. Ultrastructural characterization of dark microglia during aging in a mouse model of Alzheimer's disease pathology and in human post-mortem brain samples[J].J Neuroinflammation,2022,19:235.doi: 10.1186/s12974-022-02595-8
[21]Wang S, Sudan R, Peng V, et al. TREM2 drives microglia response to amyloid-β via SYK-dependent and-independent pathways[J]. Cell,2022,185:4153-4169.e19.
[22]Krasemann S, Madore C, Cialic R, et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases[J].Immunity, 2017,47:566-581.e9.
[23]Roseborough AD, Myers SJ, Khazaee R, et al. Plasma derived extracellular vesicle biomarkers of microglia activation in an experimental stroke model[J].J Neuroinflammation, 2023:20:20.doi: 10.1186/s12974-023-02708-x.
[24]Wang SY, Fu XX, Duan R, et al. The alzheimer's disease-associated gene TREML2 modulates inflammation by regulating microglia polarization and NLRP3 inflammasome activation[J].Neural Regen Res,2023,18:434-438.
[25]Jucker M,Walke LC.Alzheimer's disease: from immunotherapy to immunoprevention[J].Cell, 2023, 28,186:4260-4270.

小胶质细胞在阿尔茨海默病发病机制中的作用

The role of microglia in the pathogenesis of Azheimer's disease

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	肖艳红, 姜明东, 林叶远, 冉灿, 梁博. 灯盏花乙素抑制人前列腺癌细胞系PC-3的增殖和迁移[J]. 基础医学与临床, 2024, 44(9): 1229-1235.
[2]	秦晓莉, 赵琳娜, 付榕, 郭玉莹, 徐士欣. 星形胶质细胞吞噬作用在阿尔茨海默病中的研究进展[J]. 基础医学与临床, 2024, 44(8): 1180-1184.
[3]	张昊, 孙浩, 廖红. 诱导抑郁症患者小胶质细胞炎性反应的机制[J]. 基础医学与临床, 2024, 44(7): 1029-1033.
[4]	高璐, 蔡孟华, 许依, 何维, 陈慧, 张建民. 过表达膜定位IL-3的293T细胞外泌体的纯化及体外功能验证[J]. 基础医学与临床, 2024, 44(7): 947-953.
[5]	郭艳芳, 耿超, 解相宏, 陈恩惠, 郭泽宇, 张明龙, 刘晓军. Sestrin1参与调控小鼠肝脏细胞糖异生[J]. 基础医学与临床, 2024, 44(2): 141-146.
[6]	王曌慧, 刘潇, 周玥, 魏心怡, 王玥, 李俊发, 赵丽. 髓系细胞触发受体2在高糖处理的小胶质细胞中的表达及作用[J]. 基础医学与临床, 2024, 44(2): 167-173.
[7]	李奇骏, 王俊山, 袁晶, 崔瑞雪. 常见类型神经退行性痴呆的神经影像学表现[J]. 基础医学与临床, 2024, 44(12): 1741-1745.
[8]	曹培谦, 王志刚, 苗学红. 甘草酸二铵减轻肺结核模型大鼠肺损伤[J]. 基础医学与临床, 2024, 44(11): 1544-1550.
[9]	朱锋, 钟粤, 邓义江, 刘文值, 边疆. 右美托咪定通过上调PPAR-γ改善神经病理性疼痛模型大鼠的痛觉敏化[J]. 基础医学与临床, 2023, 43(9): 1369-1374.
[10]	王继辉, 曹吉烈, 张立军, 张军, 鹿文葆. TARBP2降解AKAP12转录本促进人乳腺癌细胞转移[J]. 基础医学与临床, 2023, 43(8): 1259-1264.
[11]	陈小坤, 包新杰, 高俊, 李永宁. 神经干细胞移植治疗阿尔兹海默病的机制研究进展[J]. 基础医学与临床, 2023, 43(7): 1148-1151.
[12]	刘诗雨, 刘宇健. 组织激肽释放酶8在神经系统疾病中作用的研究进展[J]. 基础医学与临床, 2023, 43(4): 660-664.
[13]	李立亚, 秦霈. 星形胶质细胞在中枢神经系统炎性疾病中作用的研究进展[J]. 基础医学与临床, 2023, 43(4): 665-668.
[14]	刘湛傲, 陈晨. 卵泡体外激活在早发性卵巢功能不全患者辅助生殖中的研究进展[J]. 基础医学与临床, 2023, 43(4): 538-546.
[15]	许津铭, 洪语萱, 韦晖, 许琪. 抗SARS-CoV-2相关线性表位抗体诱发小鼠神经炎性反应[J]. 基础医学与临床, 2023, 43(3): 438-443.