{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:16:57Z","timestamp":1791213417169,"version":"4.1.0"},"reference-count":130,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this review, we focus on the emerging roles of microglia in the brain, with particular attention to synaptic plasticity in health and disease. We present evidence that ramified microglia, classically believed to be \u201cresting\u201d (i.e., inactive), are instead strongly implicated in dynamic and plastic processes. Indeed, there is an intimate relationship between microglia and neurons at synapses which modulates activity-dependent functional and structural plasticity through the release of cytokines and growth factors. These roles are indispensable to brain development and cognitive function. Therefore, approaches aimed at maintaining the ramified state of microglia might be critical to ensure normal synaptic plasticity and cognition. On the other hand, inflammatory signals associated with Alzheimer\u2019s disease are able to modify the ramified morphology of microglia, thus leading to synapse loss and dysfunction, as well as cognitive impairment. In this context, we highlight microglial TREM2 and CSF1R as emerging targets for disease-modifying therapy in Alzheimer\u2019s disease (AD) and other neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/ijms22052342","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T09:47:20Z","timestamp":1614332840000},"page":"2342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Targeting Microglia-Synapse Interactions in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5215-3776","authenticated-orcid":false,"given":"Gaia","family":"Piccioni","sequence":"first","affiliation":[{"name":"Laboratory Pharmacology of Synaptic Plasticity, European Brain Research Institute, 00161 Rome, Italy"},{"name":"Department of Physiology and Pharmacology \u201cV.Erspamer\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalila","family":"Mango","sequence":"additional","affiliation":[{"name":"Laboratory Pharmacology of Synaptic Plasticity, European Brain Research Institute, 00161 Rome, Italy"},{"name":"School of Pharmacy, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira","family":"Saidi","sequence":"additional","affiliation":[{"name":"Laboratory Pharmacology of Synaptic Plasticity, European Brain Research Institute, 00161 Rome, Italy"},{"name":"Department of Physiology and Pharmacology \u201cV.Erspamer\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Corbo","sequence":"additional","affiliation":[{"name":"Department of Neurorehabilitation Sciences, Casa Cura Policlinico, 20144 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Nistic\u00f2","sequence":"additional","affiliation":[{"name":"Laboratory Pharmacology of Synaptic Plasticity, European Brain Research Institute, 00161 Rome, Italy"},{"name":"School of Pharmacy, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.neuron.2004.09.012","article-title":"LTP and LTD: An Embarrassment of Riches","volume":"44","author":"Malenka","year":"2004","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/361031a0","article-title":"A Synaptic Model of Memory: Long-Term Potentiation in the Hippocampus","volume":"361","author":"Bliss","year":"1993","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1126\/science.1074069","article-title":"Alzheimer\u2019s Disease Is a Synaptic Failure","volume":"298","author":"Selkoe","year":"2002","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"566","DOI":"10.3389\/fnhum.2016.00566","article-title":"The Indispensable Roles of Microglia and Astrocytes during Brain Development","volume":"10","author":"Reemst","year":"2016","journal-title":"Front. 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