{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:38:37Z","timestamp":1784133517230,"version":"3.55.0"},"reference-count":66,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31600823"],"award-info":[{"award-number":["31600823"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Niemann\u2013Pick type C disease (NPCD) is a rare and fatal lysosomal storage disorder. There are limited therapies for NPCD, although multiple small\u2010molecule compounds have shown therapeutic potential for NPCD. Curcumin (CUR), a polyphenolic compound enriched in turmeric, has cholesterol\u2010lowering effects via regulating intestinal cholesterol absorption and liver cholesterol synthesis. CUR normalises sphingolipid trafficking and stimulates exosome\/microvesicle release, increases cytosolic Ca\n                      <jats:sup>2+<\/jats:sup>\n                      levels, and enhances lysosomal activation via mTOR suppression and TFEB activation. How CUR specifically targets lysosomal cholesterol has not been fully clarified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Effects of curcumin on lysosomal cholesterol accumulation were evaluated in NPC1 cell models. Filipin staining, immunofluorescence, surface LAMP1 and NAGase activity and Cathepsin B activity were investigated to evaluate lysosomal cholesterol, TFEB translocation, lysosomal exocytosis and hydrolytic activity. Lysosomal acidification was determined by Lysotracker Red, Oregon Green, and sfGFP\/mCherry transfection. CRISPR\/Cas9 and siRNA interference were used to investigate the role of TFEB\/TFE3 and TRPML1 in curcumin\u2010induced cholesterol reduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>CUR alleviates lysosomal cholesterol accumulation in NPC1 cells in a TFEB\u2010 and TFE3\u2010dependent manner. CUR enhanced lysosomal acidity and promoted calcium\u2010dependent lysosomal exocytosis, which contributed to CUR\u2010mediated lysosomal cholesterol clearance. The combination of CUR with specific agonists (ML\u2010SAs) of MCOLN1\/TRPML1, a lysosomal cation channel required for lysosomal exocytosis, improved lysosomal cholesterol clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      CUR reduces lysosomal cholesterol accumulation in NPC1 cells by activating TFEB\/TFE3 pathways and promoting Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010 and TRPML1\u2010dependent lysosomal exocytosis. These findings support curcumin and its analogues as potential therapeutics for NPCD and other diseases of lysosomal storage.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70448","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T01:35:38Z","timestamp":1777253738000},"page":"4305-4320","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Curcumin controls lysosomal acidification and exocytosis to ameliorate lysosomal cholesterol accumulation in Niemann\u2013Pick type C disease"],"prefix":"10.1111","volume":"183","author":[{"given":"Hongyu","family":"Chen","sequence":"first","affiliation":[{"name":"Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengli","family":"Zhao","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Luo","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohe","family":"Chu","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology  Hangzhou China"},{"name":"Department of Molecular, Cellular, and Developmental Biology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"issue":"2","key":"e_1_2_12_2_1","first-page":"S374","article-title":"The Concise Guide to PHARMACOLOGY 2023\/24: Transporters","volume":"180","author":"Alexander S. 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