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Microglia express Trem2, which serves as a receptor for a multitude of ligands enhancing their phagocytic activity. Trem2 has emerged as a critical modulator of microglial activity, especially in many neurodegenerative disorders. Human\n                    <jats:italic toggle=\"yes\">TREM2<\/jats:italic>\n                    mutations are associated with an increased risk of developing Alzheimer disease (AD) and other neurodegenerative diseases. Trem2 plays dual roles in neuroinflammation and more specifically in disease-associated microglia. Most recent developments on the molecular mechanisms of Trem2, emphasizing its role in uptake and clearance of amyloid \u03b2 (A\u03b2) aggregates and other tissue debris to help protect and preserve the brain, are encouraging. Although Trem2 normally stimulates defense mechanisms, its dysregulation can intensify inflammation, which poses major therapeutic challenges. Recent therapeutic approaches targeting Trem2 via agonistic antibodies and gene therapy methodologies present possible avenues for reducing the burden of neurodegenerative diseases. This review highlights the promise of Trem2 as a therapeutic target, especially for A\u03b2-associated AD, and calls for more mechanistic investigations to understand the context-specific role of microglial Trem2 in developing effective therapies against neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.1177\/10738584241254118","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T02:42:09Z","timestamp":1716259329000},"page":"159-176","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":68,"title":["Microglia, Trem2, and Neurodegeneration"],"prefix":"10.1177","volume":"31","author":[{"given":"Qian","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Cellular and Integrative Physiology, Center for Biomedical Neuroscience, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul A.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, Center for Biomedical Neuroscience, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0989-1498","authenticated-orcid":false,"given":"Manzoor A.","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Cellular and Integrative Physiology, Center for Biomedical Neuroscience, Joe R. and Teresa Lozano Long School of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.679043"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23074"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.677286"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2114486119"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0216-6"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202216987"},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11082094"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.10.4991"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.8.1111"},{"key":"e_1_3_2_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.6237"},{"key":"e_1_3_2_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.856376"},{"key":"e_1_3_2_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05672-9"},{"key":"e_1_3_2_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1615823"},{"key":"e_1_3_2_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2015.05.010"},{"key":"e_1_3_2_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02193-z"},{"key":"e_1_3_2_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00440-9"},{"key":"e_1_3_2_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-051116-052358"},{"key":"e_1_3_2_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2020.1750388"},{"key":"e_1_3_2_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.003"},{"key":"e_1_3_2_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.003"},{"key":"e_1_3_2_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau2291"},{"key":"e_1_3_2_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav6221"},{"key":"e_1_3_2_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01980-5"},{"key":"e_1_3_2_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.04.016"},{"key":"e_1_3_2_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06494.x"},{"key":"e_1_3_2_27_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.371360"},{"key":"e_1_3_2_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI138179"},{"key":"e_1_3_2_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-023-06729-5"},{"key":"e_1_3_2_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.06.005"},{"issue":"16","key":"e_1_3_2_31_1","article-title":"TREM2 and neurodegenerative disease","volume":"369","author":"Guerreiro R","year":"2013","unstructured":"Guerreiro R, Hardy J. 2013. 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