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Targeting histone deacetylase\u201011 (HDAC11) offers a novel therapeutic strategy due to its role in immune regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We conducted neuropathological analyses on human AD\n                      <jats:italic>post mortem<\/jats:italic>\n                      brain tissues and 5xFAD transgenic mice. We developed PB94, a brain\u2010permeable HDAC11\u2010selective inhibitor, and assessed its effects using live\u2010animal imaging and behavioral studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>HDAC11 was significantly upregulated in AD brains, correlating with amyloid pathology and neuroinflammatory markers. PB94 treatment reduced amyloid burden and neuroinflammation, improving cognitive function in 5xFAD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our findings highlight HDAC11 as a promising drug target for AD. PB94's ability to reduce amyloid pathology and neuroinflammation suggests its potential as an effective therapeutic. This study supports further exploration of HDAC11 inhibition as a treatment strategy for AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Histone deacetylase\u201011 (HDAC11) is significantly upregulated in Alzheimer's disease (AD) brains and colocalizes with amyloid pathology and neuroinflammatory markers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Novel brain\u2010permeable HDAC11\u2010selective inhibitor PB94 demonstrates promising therapeutic potential for AD treatment.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>PB94 treatment reduces amyloid burden and neuroinflammation in AD mouse models, confirmed by live imaging studies.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>HDAC11 inhibition enhances microglial phagocytosis of amyloid beta proteins and modulates inflammatory cytokine levels.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>PB94 treatment improves cognitive function in AD mouse models while showing favorable brain penetration and selectivity.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14616","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T03:44:53Z","timestamp":1742442293000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["HDAC11 displays neuropathological alterations and offers as a novel drug target for Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Ping","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Targeted Tracer Research and Development Laboratory West China Hospital, Sichuan University  Chengdu China"},{"name":"Athinoula A. Martinos Center for Biomedical Imaging Department of Radiology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasenjit","family":"Mondal","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit, McCance Center for Brain Health Mass General Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging Department of Radiology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Gomm","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit, McCance Center for Brain Health Mass General Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Suen","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit, McCance Center for Brain Health Mass General Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuyue","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyue","family":"Zhu","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging Department of Radiology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoqi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongzhao","family":"Ran","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit, McCance Center for Brain Health Mass General Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqian","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Anesthesia Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolph E.","family":"Tanzi","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit, McCance Center for Brain Health Mass General Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Zhang","sequence":"additional","affiliation":[{"name":"Genetics and Aging Research Unit, McCance Center for Brain Health Mass General Institute for Neurodegenerative Disease Department of Neurology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changning","family":"Wang","sequence":"additional","affiliation":[{"name":"Athinoula A. 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