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调控小胶质细胞干预阿尔茨海默病的研究进展

常远, Mageta SamwelMAGETA, 李倪博文, 汤迎琦, 李黄娟, 钱程根

常远,Mageta Samwel MAGETA,李倪博文,等. 调控小胶质细胞干预阿尔茨海默病的研究进展[J]. 中国药科大学学报,2024,55(5):603 − 612. DOI: 10.11665/j.issn.1000-5048.2024030201
引用本文: 常远,Mageta Samwel MAGETA,李倪博文,等. 调控小胶质细胞干预阿尔茨海默病的研究进展[J]. 中国药科大学学报,2024,55(5):603 − 612. DOI: 10.11665/j.issn.1000-5048.2024030201
CHANG Yuan, MAGETA Mageta Samwel, LI Nibowen, et al. Research advances in modulating microglia for intervening in Alzheimer’s disease[J]. J China Pharm Univ, 2024, 55(5): 603 − 612. DOI: 10.11665/j.issn.1000-5048.2024030201
Citation: CHANG Yuan, MAGETA Mageta Samwel, LI Nibowen, et al. Research advances in modulating microglia for intervening in Alzheimer’s disease[J]. J China Pharm Univ, 2024, 55(5): 603 − 612. DOI: 10.11665/j.issn.1000-5048.2024030201

调控小胶质细胞干预阿尔茨海默病的研究进展

基金项目: 国家自然科学基金项目(No. 82072069);江苏省优秀青年基金项目(BK20220153)
详细信息
    作者简介:

    钱程根,博士,中国药科大学药学院副教授,博士生导师。江苏省优秀青年基金、江苏省双创博士、江苏省优秀博士论文和南京大学优秀博士论文获得者。从事药物制剂、生物功能材料及化学生物学等交叉领域的研究,近年主要关注肿瘤免疫治疗和阿尔茨海默病早期诊断和治疗研究。近年来在National Science ReviewPNASScience AdvancesAdvanced MaterialsAdvanced Functional MaterialsAngewandte Chemie International EditionACS NanoNano Letters等国际权威杂志共发表同行评议论文43篇,其中(共同)第一或通信作者发表论文14篇(8篇IF>10),总引用3400余次,单篇最高引用438次,H-index为29(来源:Google scholar),申请中国发明专利5项。其中,发表在Advanced MaterialsAngewandte Chemie International EditionChemistry-A European Journal的文章分别被选为封面文章或热点文章;目前3篇文章曾被选为ESI高被引论文

    通讯作者:

    钱程根: Tel:13400063258 E-mail:cgqian@cpu.edu.cn

  • 中图分类号: R965;R749

Research advances in modulating microglia for intervening in Alzheimer’s disease

Funds: This study was supported by the National Natural Science Foundation of China (No. 82072069) and the Jiangsu Fund for Excellent Young (No. BK20220153)
  • 摘要:

    阿尔茨海默病(Alzheimer’s disease, AD)是世界上最常见的以痴呆为主要表现形式的神经退行性疾病。以免疫细胞小胶质细胞为靶点的病理调控在治疗AD方面显示出独特优势,能够在早期阻止AD的病理进展。本文首先概述小胶质细胞在AD发病机制中的作用,然后总结小胶质细胞在AD中与常见关键病理Aβ、tau蛋白、神经炎症以及能量代谢障碍的关系,最后综述基于小胶质细胞为靶点以逆转AD病理的可行干预策略,并探讨各项研究目前仍需要改进的问题,旨在加深对调控小胶质细胞干预AD病理的策略了解,为 未来AD患者的早期干预和治疗提供新的思路。

    Abstract:

    Alzheimer’s disease (AD) is the most common neurodegenerative disease in the world with dementia as its main manifestation. The pathological regulation strategies based on microglia in immune cells have shown their unique advantages in treating AD by preventing the pathological progression of AD at an early stage. This paper firstly introduces the role of microglia in the pathogenesis of AD, then summarizes the relationship between microglia and the common key pathologies of Aβ, tau proteins, neuroinflammation, and impaired energy metabolism in AD, and finally reviews feasible microglia-targeted intervention strategies against AD with some discussion about some current issues for improvement in each study, in the hope of deepening the understanding of strategies that regulate microglia to block AD pathology and providing some new ideas for the early intervention and treatment of AD patients in the future.

  • 图  1   调控小胶质细胞干预AD病理进展途径的示意图

    A:抗体介导小胶质细胞对Aβ的识别;B:调控小胶质细胞的表型(如TREM2)促进其吞噬和降解Aβ的能力;C:抑制小胶质细胞外泌体途径介导Aβ/tau蛋白的再传播;D:抑制小胶质细胞的神经炎症减少神经损伤;E:调控小胶质细胞的能量代谢途径恢复其功能,通过干预异常变化的葡萄糖、脂质、氨基酸代谢过程,恢复小胶质细胞正常功能ROS:活性氧;NLRP3:炎性小体;IL-1β:白细胞介素-1;DAP12:DNAX活化蛋白12;TREM2:髓样细胞触发受体 2

    表  1   参与AD病理的小胶质细胞免疫受体靶点

    靶点表达水平机制动物模型作用效果参考文献
    TRPV1功能失调介导钙信号转导,调控细胞生理活动1.SpragueDawley大鼠
    2.TRPV1-/-的C57BL/6J
    1.过度激活引起线粒体损伤和细胞色素c释放引起损伤;2.诱导自噬,增加突触可塑性,降低Aβ/tau蛋白水平[4647]
    CD33表达上调结合唾液酸并募集蛋白磷酸酶SHP1和SHP2传递细胞内抑制信号APPswe/PS1dE9AD风险基因,抑制摄取Aβ
    [4849]
    TREM2功能缺陷通过相关的信号转导接头DAP12传输细胞内信号APPswe/PS1dE9促进对Aβ吞噬清除,降低Aβ沉积和神经炎症
    [45,50]
    TLR功能改变识别PAMPs和DAMPs,激活干扰素调节因子(IRF)和NF-κB通路TLR-/-的C57BL/6JTLR2参与Aβ引起的小胶质细胞活化并介导神经炎症[5152]
    P2X7R表达上调感知炎症相关的细胞外ATP水平,调控多种生理过程P2X7REGFP
    APPswe/PS1dE9
    P301S
    参与激活诱导ROS产生放大神经炎症,降低对Aβ的吞噬,加剧神经元损伤,阻断可以减少tau蛋白积累[5355]
    RAGE表达上调通过多种途径上调炎症通路5xFAD
    mhAPP
    1.介导Aβ引起的应激相关激酶的激活加剧突触缺陷;2.驱动Aβ的线粒体靶向加剧炎症[5657]
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  • [1]

    Knopman DS, Amieva H, Petersen RC, et al. Alzheimer disease[J]. Nat Rev Dis Primers, 2021, 7(1): 33. doi: 10.1038/s41572-021-00269-y

    [2]

    Huang LK, Kuan YC, Lin HW, et al. Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update[J]. J Biomed Sci, 2023, 30(1): 83. doi: 10.1186/s12929-023-00976-6

    [3]

    Long JM, Holtzman DM. Alzheimer disease: an update on pathobiology and treatment strategies[J]. Cell, 2019, 179(2): 312-339. doi: 10.1016/j.cell.2019.09.001

    [4]

    Livingston G, Huntley J, Sommerlad A, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission[J]. Lancet, 2020, 396(10248): 413-446. doi: 10.1016/S0140-6736(20)30367-6

    [5]

    Leng FD, Edison P. Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here[J]? Nat Rev Neurol, 2021, 17(3): 157-172. doi: 10.1038/s41582-020-00435-y

    [6]

    Cummings J, Feldman HH, Scheltens P. The “rights” of precision drug development for Alzheimer’s disease[J]. Alzheimers Res Ther, 2019, 11(1): 76. doi: 10.1186/s13195-019-0529-5

    [7]

    Salter MW, Stevens B. Microglia emerge as central players in brain disease[J]. Nat Med, 2017, 23(9): 1018-1027. doi: 10.1038/nm.4397

    [8]

    Askew K, Li KZ, Olmos-Alonso A, et al. Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain[J]. Cell Rep, 2017, 18(2): 391-405. doi: 10.1016/j.celrep.2016.12.041

    [9]

    Hickman S, Izzy S, Sen P, et al. Microglia in neurodegeneration[J]. Nat Neurosci, 2018, 21(10): 1359-1369. doi: 10.1038/s41593-018-0242-x

    [10]

    Lauro C, Limatola C. Metabolic reprograming of microglia in the regulation of the innate inflammatory response[J]. Front Immunol, 2020, 11: 493. doi: 10.3389/fimmu.2020.00493

    [11]

    Chen GF, Xu TH, Yan Y, et al. Amyloid beta: structure, biology and structure-based therapeutic development[J]. Acta Pharmacol Sin, 2017, 38(9): 1205-1235. doi: 10.1038/aps.2017.28

    [12]

    Griciuc A, Patel S, Federico AN, et al. TREM2 acts downstream of CD33 in modulating microglial pathology in Alzheimer’s disease[J]. Neuron, 2019, 103(5): 820-835. e7. doi: 10.1016/j.neuron.2019.06.010

    [13]

    Pankiewicz JE, Diaz JR, Martá-Ariza M, et al. Peroxiredoxin 6 mediates protective function of astrocytes in Aβ proteostasis[J]. Mol Neurodegener, 2020, 15(1): 50. doi: 10.1186/s13024-020-00401-8

    [14]

    Quick JD, Silva C, Wong JH, et al. Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration[J]. J Neuroinflammation, 2023, 20(1): 185. doi: 10.1186/s12974-023-02866-y

    [15]

    Mustaly-Kalimi S, Gallegos W, Marr RA, et al. Protein mishandling and impaired lysosomal proteolysis generated through calcium dysregulation in Alzheimer’s disease[J]. Proc Natl Acad Sci U S A, 2022, 119(49): e2211999119. doi: 10.1073/pnas.2211999119

    [16]

    Hao YN, Su C, Liu XT, et al. Bioengineered microglia-targeted exosomes facilitate Aβ clearance via enhancing activity of microglial lysosome for promoting cognitive recovery in Alzheimer’s disease[J]. Biomater Adv, 2022, 136: 212770. doi: 10.1016/j.bioadv.2022.212770

    [17]

    Sjölin K, Kultima K, Larsson A, et al. Distribution of five clinically important neuroglial proteins in the human brain[J]. Mol Brain, 2022, 15(1): 52. doi: 10.1186/s13041-022-00935-6

    [18]

    Moloney CM, Lowe VJ, Murray ME. Visualization of neurofibrillary tangle maturity in Alzheimer’s disease: a clinicopathologic perspective for biomarker research[J]. Alzheimers Dement, 2021, 17(9): 1554-1574. doi: 10.1002/alz.12321

    [19]

    Brunello CA, Merezhko M, Uronen RL, et al. Mechanisms of secretion and spreading of pathological tau protein[J]. Cell Mol Life Sci, 2020, 77(9): 1721-1744. doi: 10.1007/s00018-019-03349-1

    [20]

    Hopp SC, Lin Y, Oakley D, et al. The role of microglia in processing and spreading of bioactive tau seeds in Alzheimer’s disease[J]. J Neuroinflammation, 2018, 15(1): 269. doi: 10.1186/s12974-018-1309-z

    [21]

    Ising C, Venegas C, Zhang SS, et al. NLRP3 inflammasome activation drives tau pathology[J]. Nature, 2019, 575(7784): 669-673. doi: 10.1038/s41586-019-1769-z

    [22]

    Busche MA, Hyman BT. Synergy between amyloid-β and tau in Alzheimer’s disease[J]. Nat Neurosci, 2020, 23(10): 1183-1193. doi: 10.1038/s41593-020-0687-6

    [23]

    Pascoal TA, Benedet al, Ashton NJ, et al. Microglial activation and tau propagate jointly across Braak stages[J]. Nat Med, 2021, 27(9): 1592-1599. doi: 10.1038/s41591-021-01456-w

    [24]

    Congdon EE, Ji CY, Tetlow AM, et al. Tau-targeting therapies for Alzheimer disease: current status and future directions[J]. Nat Rev Neurol, 2023, 19(12): 715-736. doi: 10.1038/s41582-023-00883-2

    [25]

    Wang CC, Zong S, Cui XL, et al. The effects of microglia-associated neuroinflammation on Alzheimer’s disease[J]. Front Immunol, 2023, 14: 1117172. doi: 10.3389/fimmu.2023.1117172

    [26]

    Zhang WF, Xiao D, Mao QW, et al. Role of neuroinflammation in neurodegeneration development[J]. Signal Transduct Target Ther, 2023, 8(1): 267. doi: 10.1038/s41392-023-01486-5

    [27]

    Dhapola R, Hota SS, Sarma P, et al. Recent advances in molecular pathways and therapeutic implications targeting neuroinflammation for Alzheimer’s disease[J]. Inflammopharmacology, 2021, 29(6): 1669-1681. doi: 10.1007/s10787-021-00889-6

    [28]

    Thawkar BS, Kaur G. Inhibitors of NF-κB and P2X7/NLRP3/Caspase 1 pathway in microglia: novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer’s disease[J]. J Neuroimmunol, 2019, 326: 62-74. doi: 10.1016/j.jneuroim.2018.11.010

    [29]

    Bairamian D, Sha S, Rolhion N, et al. Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease[J]. Mol Neurodegener, 2022, 17(1): 19. doi: 10.1186/s13024-022-00522-2

    [30]

    Cunnane SC, Trushina E, Morland C, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing[J]. Nat Rev Drug Discov, 2020, 19(9): 609-633. doi: 10.1038/s41573-020-0072-x

    [31]

    Li Y, Xia XH, Wang Y, et al. Mitochondrial dysfunction in microglia: a novel perspective for pathogenesis of Alzheimer’s disease[J]. J Neuroinflammation, 2022, 19(1): 248. doi: 10.1186/s12974-022-02613-9

    [32]

    Baik SH, Kang S, Lee W, et al. A breakdown in metabolic reprogramming causes microglia dysfunction in Alzheimer’s disease[J]. Cell Metab, 2019, 30(3): 493-507. e6. doi: 10.1016/j.cmet.2019.06.005

    [33]

    Hu YL, Mai WH, Chen LH, et al. mTOR-mediated metabolic reprogramming shapes distinct microglia functions in response to lipopolysaccharide and ATP[J]. Glia, 2020, 68(5): 1031-1045. doi: 10.1002/glia.23760

    [34]

    Toledo JB, Arnold M, Kastenmüller G, et al. Metabolic network failures in Alzheimer’s disease: a biochemical roadmap[J]. Alzheimers Dement, 2017, 13(9): 965-984. doi: 10.1016/j.jalz.2017.01.020

    [35]

    Lemere CA. Immunotherapy for Alzheimer’s disease: hoops and hurdles[J]. Mol Neurodegener, 2013, 8: 36. doi: 10.1186/1750-1326-8-36

    [36]

    Solito E, Sastre M. Microglia function in Alzheimer’s disease[J]. Front Pharmacol, 2012, 3: 14.

    [37]

    Hu J, Chen Q, Zhu HR, et al. Microglial Piezo1 senses Aβ fibril stiffness to restrict Alzheimer’s disease[J]. Neuron, 2023, 111(1): 15-29. e8. doi: 10.1016/j.neuron.2022.10.021

    [38]

    Adolfsson O, Pihlgren M, Toni N, et al. An effector-reduced anti-β-amyloid (Aβ) antibody with unique aβ binding properties promotes neuroprotection and glial engulfment of Aβ[J]. J Neurosci, 2012, 32(28): 9677-9689. doi: 10.1523/JNEUROSCI.4742-11.2012

    [39]

    Morgan D. Mechanisms of Aβ plaque clearance following passive Aβ immunization[J]. Neurodegener Dis, 2005, 2(5): 261-266. doi: 10.1159/000090366

    [40]

    Jucker M, Walker LC. Alzheimer’s disease: from immunotherapy to immunoprevention[J]. Cell, 2023, 186(20): 4260-4270. doi: 10.1016/j.cell.2023.08.021

    [41]

    Wang QQ, Yao HM, Liu WY, et al. Microglia polarization in Alzheimer’s disease: mechanisms and a potential therapeutic target[J]. Front Aging Neurosci, 2021, 13: 772717. doi: 10.3389/fnagi.2021.772717

    [42]

    Ren CX, Li DD, Zhou QX, et al. Mitochondria-targeted TPP-MoS2 with dual enzyme activity provides efficient neuroprotection through M1/M2 microglial polarization in an Alzheimer’s disease model[J]. Biomaterials, 2020, 232: 119752. doi: 10.1016/j.biomaterials.2019.119752

    [43]

    Liu PX, Zhang TY, Chen QJ, et al. Biomimetic dendrimer-peptide conjugates for early multi-target therapy of Alzheimer’s disease by inflammatory microenvironment modulation[J]. Adv Mater, 2021, 33(26): e2100746. doi: 10.1002/adma.202100746

    [44]

    Daniel Lee CYD, Daggett A, Gu XF, et al. Elevated TREM2 gene dosage reprograms microglia responsivity and ameliorates pathological phenotypes in Alzheimer’s disease models[J]. Neuron, 2018, 97(5): 1032-1048. e5.

    [45]

    Jiang T, Tan L, Zhu XC, et al. Upregulation of TREM2 ameliorates neuropathology and rescues spatial cognitive impairment in a transgenic mouse model of Alzheimer’s disease[J]. Neuropsychopharmacology, 2014, 39(13): 2949-2962. doi: 10.1038/npp.2014.164

    [46]

    Wang CF, Huang W, Lu J, et al. TRPV1-mediated microglial autophagy attenuates Alzheimer’s disease-associated pathology and cognitive decline[J]. Front Pharmacol, 2021, 12: 763866.

    [47]

    Kim SR, Kim SU, Oh U, et al. Transient receptor potential vanilloid subtype 1 mediates microglial cell death in vivo and in vitro via Ca2+-mediated mitochondrial damage and cytochrome c release[J]. J Immunol, 2006, 177(7): 4322-4329. doi: 10.4049/jimmunol.177.7.4322

    [48]

    Linnartz-Gerlach B, Mathews M, Neumann H. Sensing the neuronal glycocalyx by glial sialic acid binding immunoglobulin-like lectins[J]. Neuroscience, 2014, 275: 113-124. doi: 10.1016/j.neuroscience.2014.05.061

    [49]

    Griciuc A, Serrano-Pozo A, Parrado AR, et al. Alzheimer’s disease risk gene CD33 inhibits microglial uptake of amyloid beta[J]. Neuron, 2013, 78(4): 631-643. doi: 10.1016/j.neuron.2013.04.014

    [50]

    Lanier LL. DAP10- and DAP12-associated receptors in innate immunity[J]. Immunol Rev, 2009, 227(1): 150-160. doi: 10.1111/j.1600-065X.2008.00720.x

    [51]

    Reed-Geaghan EG, Savage JC, Hise AG, et al. CD14 and toll-like receptors 2 and 4 are required for fibrillar Aβ-stimulated microglial activation[J]. J Neurosci, 2009, 29(38): 11982-11992. doi: 10.1523/JNEUROSCI.3158-09.2009

    [52]

    Gay NJ, Symmons MF, Gangloff M, et al. Assembly and localization of Toll-like receptor signalling complexes[J]. Nat Rev Immunol, 2014, 14(8): 546-558. doi: 10.1038/nri3713

    [53]

    Brandao-Burch A, Key ML, Patel JJ, et al. The P2X7 receptor is an important regulator of extracellular ATP levels[J]. Front Endocrinol, 2012, 3: 41.

    [54]

    Martínez-Frailes C, di Lauro C, Bianchi C, et al. Amyloid peptide induced neuroinflammation increases the P2X7 receptor expression in microglial cells, impacting on its functionality[J]. Front Cell Neurosci, 2019, 13: 143.

    [55]

    Ruan Z, Delpech JC, Venkatesan Kalavai S, et al. P2RX7 inhibitor suppresses exosome secretion and disease phenotype in P301S tau transgenic mice[J]. Mol Neurodegener, 2020, 15(1): 47. doi: 10.1186/s13024-020-00396-2

    [56]

    Sbai O, Djelloul M, Auletta A, et al. AGE-TXNIP axis drives inflammation in Alzheimer’s by targeting Aβ to mitochondria in microglia[J]. Cell Death Dis, 2022, 13(4): 302. doi: 10.1038/s41419-022-04758-0

    [57]

    Criscuolo C, Fontebasso V, Middei S, et al. Entorhinal Cortex dysfunction can be rescued by inhibition of microglial RAGE in an Alzheimer’s disease mouse model[J]. Sci Rep, 2017, 7: 42370. doi: 10.1038/srep42370

    [58]

    Rajendran L, Honsho M, Zahn TR, et al. Alzheimer’s disease β-amyloid peptides are released in association with exosomes[J]. Proc Natl Acad Sci U S A, 2006, 103(30): 11172-11177. doi: 10.1073/pnas.0603838103

    [59]

    Yuyama K, Sun H, Sakai S, et al. Decreased amyloid-β pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice[J]. J Biol Chem, 2014, 289(35): 24488-24498. doi: 10.1074/jbc.M114.577213

    [60]

    Polanco JC, Scicluna BJ, Hill AF, et al. Extracellular vesicles isolated from the brains of rTg4510 mice seed tau protein aggregation in a threshold-dependent manner[J]. J Biol Chem, 2016, 291(24): 12445-12466. doi: 10.1074/jbc.M115.709485

    [61]

    Elsherbini A, Kirov AS, Dinkins MB, et al. Association of aβ with ceramide-enriched astrosomes mediates aβ neurotoxicity[J]. Acta Neuropathol Commun, 2020, 8(1): 60. doi: 10.1186/s40478-020-00931-8

    [62]

    Wang GH, Dinkins M, He Q, et al. Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4): potential mechanism of apoptosis induction in Alzheimer disease (AD)[J]. J Biol Chem, 2012, 287(25): 21384-21395. doi: 10.1074/jbc.M112.340513

    [63]

    Dinkins MB, Dasgupta S, Wang GH, et al. Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer’s disease[J]. Neurobiol Aging, 2014, 35(8): 1792-1800. doi: 10.1016/j.neurobiolaging.2014.02.012

    [64]

    Asai H, Ikezu S, Tsunoda S, et al. Depletion of microglia and inhibition of exosome synthesis halt tau propagation[J]. Nat Neurosci, 2015, 18(11): 1584-1593. doi: 10.1038/nn.4132

    [65]

    Zhu B, Liu Y, Hwang S, et al. Trem2 deletion enhances tau dispersion and pathology through microglia exosomes[J]. Mol Neurodegener, 2022, 17(1): 58. doi: 10.1186/s13024-022-00562-8

    [66]

    Philippens IH, Ormel PR, Baarends G, et al. Acceleration of amyloidosis by inflammation in the amyloid-beta marmoset monkey model of Alzheimer’s disease[J]. J Alzheimers Dis, 2017, 55(1): 101-113.

    [67]

    Yao J, Wang Z, Song WH, et al. Targeting NLRP3 inflammasome for neurodegenerative disorders[J]. Mol Psychiatry, 2023, 28(11): 4512-4527. doi: 10.1038/s41380-023-02239-0

    [68]

    Venegas C, Kumar S, Franklin BS, et al. Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease[J]. Nature, 2017, 552(7685): 355-361. doi: 10.1038/nature25158

    [69]

    Park MH, Lee MS, Nam G, et al. N, N'-Diacetyl-p-phenylenediamine restores microglial phagocytosis and improves cognitive defects in Alzheimer’s disease transgenic mice[J]. Proc Natl Acad Sci U S A, 2019, 116(47): 23426-23436. doi: 10.1073/pnas.1916318116

    [70]

    Pan RY, Ma J, Kong XX, et al. Sodium rutin ameliorates Alzheimer’s disease-like pathology by enhancing microglial amyloid-β clearance[J]. Sci Adv, 2019, 5(2): eaau6328. doi: 10.1126/sciadv.aau6328

    [71]

    Zhang MR, Chen HQ, Zhang WL, et al. Biomimetic remodeling of microglial riboflavin metabolism ameliorates cognitive impairment by modulating neuroinflammation[J]. Adv Sci, 2023, 10(12): e2300180. doi: 10.1002/advs.202300180

    [72]

    Yang F, Zhao DJ, Cheng M, et al. mTOR-mediated immunometabolic reprogramming nanomodulators enable sensitive switching of energy deprivation-induced microglial polarization for Alzheimer’s disease management[J]. ACS Nano, 2023, 17(16): 15724-15741. doi: 10.1021/acsnano.3c03232

    [73]

    van Lengerich B, Zhan LH, Xia D, et al. A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer’s disease models[J]. Nat Neurosci, 2023, 26(3): 416-429.

    [74]

    Shan C, Zhang D, Ma DN, et al. Osteocalcin ameliorates cognitive dysfunctions in a mouse model of Alzheimer’s Disease by reducing amyloid β burden and upregulating glycolysis in neuroglia[J]. Cell Death Discov, 2023, 9(1): 46. doi: 10.1038/s41420-023-01343-y

    [75]

    Fairley LH, Lai KO, Wong JH, et al. Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer’s disease[J]. Proc Natl Acad Sci U S A, 2023, 120(8): e2209177120. doi: 10.1073/pnas.2209177120

    [76]

    Leng LG, Yuan ZQ, Pan RY, et al. Microglial hexokinase 2 deficiency increases ATP generation through lipid metabolism leading to β-amyloid clearance[J]. Nat Metab, 2022, 4(10): 1287-1305. doi: 10.1038/s42255-022-00643-4

    [77]

    Claes C, Danhash EP, Hasselmann J, et al. Plaque-associated human microglia accumulate lipid droplets in a chimeric model of Alzheimer’s disease[J]. Mol Neurodegener, 2021, 16(1): 50. doi: 10.1186/s13024-021-00473-0

    [78]

    Victor MB, Leary N, Luna X, et al. Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity[J]. Cell Stem Cell, 2022, 29(8): 1197-1212. e8.

    [79]

    Bordone MP, Salman MM, Titus HE, et al. The energetic brain–A review from students to students[J]. J Neurochem, 2019, 151(2): 139-165. doi: 10.1111/jnc.14829

    [80]

    Tannahill GM, Curtis AM, Adamik J, et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α[J]. Nature, 2013, 496(7444): 238-242. doi: 10.1038/nature11986

    [81]

    Czapski GA, Strosznajder JB. Glutamate and GABA in microglia-neuron cross-talk in Alzheimer’s disease[J]. Int J Mol Sci, 2021, 22(21): 11677. doi: 10.3390/ijms222111677

    [82]

    Chen HL, Guo ZC, Sun YX, et al. The immunometabolic reprogramming of microglia in Alzheimer’s disease[J]. Neurochem Int, 2023, 171: 105614. doi: 10.1016/j.neuint.2023.105614

    [83]

    Yang S, Qin C, Hu ZW, et al. Microglia reprogram metabolic profiles for phenotype and function changes in central nervous system[J]. Neurobiol Dis, 2021, 152: 105290. doi: 10.1016/j.nbd.2021.105290

    [84]

    Pan RY, He L, Zhang J, et al. Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer’s disease[J]. Cell Metab, 2022, 34(4): 634-648. e6.

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    1. 王欣波,齐明明,邵音,赵宇,朴勇洙. 基于代谢组学分析安神定志方抑制神经炎症治疗阿尔茨海默病的机制研究. 海南医科大学学报. 2025(08): 589-598 . 百度学术

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  • 收稿日期:  2024-03-01
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