{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T09:30:54Z","timestamp":1793179854957,"version":"4.5.0"},"reference-count":77,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00345742"],"award-info":[{"award-number":["RS-2024-00345742"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00399237"],"award-info":[{"award-number":["RS-2024-00399237"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-02263016"],"award-info":[{"award-number":["RS-2025-02263016"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alzheimer's disease (AD) is marked by amyloid-\u03b2 (A\u03b2) accumulation, tau pathology and neuroinflammation. The \u03b2-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key driver of A\u03b2 production, while the NLRP3 inflammasome mediates microglial inflammatory responses. Histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase, is upregulated in AD, yet its role in disease mechanisms remains unclear.<\/jats:p>\n                  <jats:p>Here, we show that HDAC6 promotes BACE1 protein stability through direct deacetylation of its C-terminal lysine (K501), thereby increasing A\u03b2 production. HDAC6 also facilitated NLRP3 inflammasome activation in microglia, increasing IL-1\u03b2 production in a catalytic domain-dependent manner. HDAC6 deficiency in 5xFAD mice reduced BACE1 accumulation, A\u03b2 deposition, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) speck formation and IL-1\u03b2 levels, accompanied by improved cognitive performance. Transcriptomic profiling further revealed downregulation of disease-associated microglial and neurotoxic astrocyte signatures alongside enrichment of synaptic pathways.<\/jats:p>\n                  <jats:p>These findings establish HDAC6 as a dual regulator of A\u03b2 production and neuroinflammation, highlighting it as a promising therapeutic target in AD.<\/jats:p>","DOI":"10.1093\/brain\/awag089","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T12:45:42Z","timestamp":1772714742000},"source":"Crossref","is-referenced-by-count":4,"title":["HDAC6 regulates BACE1 stability and NLRP3 inflammasome activation in Alzheimer's disease"],"prefix":"10.1093","author":[{"given":"Jeongmi","family":"Lee","sequence":"first","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University , Suwon 16419 ,","place":["Republic of 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Sungkyunkwan University , Suwon 16419 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hyun","family":"Jun","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University , Suwon 16419 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell K P","family":"Lai","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University , Suwon 16419 ,","place":["Republic of Korea"]},{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine , Singapore 117600 ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiruma V","family":"Arumugam","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University , Suwon 16419 ,","place":["Republic of Korea"]},{"name":"Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and 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