{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:04:03Z","timestamp":1790247843624,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI Grant","doi-asserted-by":"publisher","award":["JP22H02999"],"award-info":[{"award-number":["JP22H02999"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Minocycline, a second-generation tetracycline antibiotic, has attracted interest as a CNS-active anti-inflammatory agent because it crosses the blood\u2013brain barrier and inhibits microglial activation. This review summarizes preclinical and clinical evidence for minocycline in neuroinflammation-related neuropsychiatric disorders, focusing on Alzheimer\u2019s disease (AD), Lewy body disease (LBD), schizophrenia, and major depressive disorder (MDD). Across these disorders, preclinical studies have generally shown that minocycline attenuates microglial activation or maladaptive microglial responses and improves disease-relevant behavioral, synaptic, or neuropathological outcomes. However, clinical translation has been inconsistent. Clinical trials in AD, related parkinsonian disorders, schizophrenia, and MDD have failed to demonstrate robust and reproducible efficacy, despite encouraging preclinical findings. Moreover, direct clinical evidence that minocycline suppresses microglial activation in the human brain remains very limited. These discrepancies between preclinical findings and clinical evidence may reflect heterogeneity in disease stage and microglial states, suboptimal timing of intervention, lack of direct evidence that minocycline suppresses microglial activation in the human brain, and its non-selective anti-inflammatory actions. Future studies should incorporate biomarker-based patient stratification and direct measures of central microglial target engagement.<\/jats:p>","DOI":"10.3390\/ijms27198533","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:16:28Z","timestamp":1790244988000},"page":"8533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Minocycline-Mediated Inhibition of Microglial Activation in Neuroinflammation-Related Neuropsychiatric Disorders: Preclinical Promise and Clinical Limitations"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2794-0417","authenticated-orcid":false,"given":"Sadayuki","family":"Hashioka","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa 078-8510, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/bph.12139","article-title":"Minocycline: Far beyond an antibiotic","volume":"169","author":"Zarzuelo","year":"2013","journal-title":"Br. 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