{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:46:31Z","timestamp":1760121991798,"version":"build-2065373602"},"reference-count":105,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"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>Fabry disease is a lysosomal storage disease caused by mutations in the GLA gene that encodes alpha-galactosidase (AGAL). The disease causes abnormal globotriaosylceramide (Gb3) storage in the lysosomes. Variants responsible for the genotypic spectrum of Fabry disease include mutations that abolish enzymatic activity and those that cause protein instability. The latter can be successfully treated with small molecules that either bind and stabilize AGAL or indirectly improve its cellular activity. This paper describes the first attempt to reposition curcumin, a nutraceutical, to treat Fabry disease. We tested the efficacy of curcumin in a cell model and found an improvement in AGAL activity for 80% of the tested mutant genotypes (four out of five tested). The fold-increase was dependent on the mutant and ranged from 1.4 to 2.2. We produced evidence that supports a co-chaperone role for curcumin when administered with AGAL pharmacological chaperones (1-deoxygalactonojirimycin and galactose). The combined treatment with curcumin and either pharmacological chaperone was beneficial for four out of five tested mutants and showed fold-increases ranging from 1.1 to 2.3 for DGJ and from 1.1 to 2.8 for galactose. Finally, we tested a long-term treatment on one mutant (L300F) and detected an improvement in Gb3 clearance and lysosomal markers (LAMP-1 and GAA). Altogether, our findings confirmed the necessity of personalized therapies for Fabry patients and paved the way to further studies and trials of treatments for Fabry disease.<\/jats:p>","DOI":"10.3390\/ijms24021095","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T01:48:19Z","timestamp":1672969699000},"page":"1095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Curcumin Has Beneficial Effects on Lysosomal Alpha-Galactosidase: Potential Implications for the Cure of Fabry Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3136-2138","authenticated-orcid":false,"given":"Maria","family":"Monticelli","sequence":"first","affiliation":[{"name":"Department of Biology, University of Napoli \u201cFederico II\u201d, Complesso Universitario Monte Sant\u2019Angelo, Via Cinthia, 80126 Napoli, Italy"},{"name":"Institute of Biomolecular Chemistry ICB, CNR, Via Campi Flegrei 34, 80078 Pozzuoli, Italy"},{"name":"Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies (DiSTABiF), University of Campania \u201cLuigi Vanvitelli\u201d, Via Vivaldi 43, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-183X","authenticated-orcid":false,"given":"Bruno","family":"Hay Mele","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Napoli \u201cFederico II\u201d, Complesso Universitario Monte Sant\u2019Angelo, Via Cinthia, 80126 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3693-2515","authenticated-orcid":false,"given":"Mariateresa","family":"Allocca","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry ICB, CNR, Via Campi Flegrei 34, 80078 Pozzuoli, Italy"},{"name":"Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies (DiSTABiF), University of Campania \u201cLuigi Vanvitelli\u201d, Via Vivaldi 43, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8480-0501","authenticated-orcid":false,"given":"Ludovica","family":"Liguori","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry ICB, CNR, Via Campi Flegrei 34, 80078 Pozzuoli, Italy"},{"name":"Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies (DiSTABiF), University of Campania \u201cLuigi Vanvitelli\u201d, Via Vivaldi 43, 81100 Caserta, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8061-5798","authenticated-orcid":false,"given":"Jan","family":"Lukas","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht-Kossel\u201d, Department of Neurology, University Medical Center Rostock, 18147 Rostock, Germany"},{"name":"Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, 18147 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1337-2909","authenticated-orcid":false,"given":"Maria Chiara","family":"Monti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-0297","authenticated-orcid":false,"given":"Elva","family":"Morretta","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6147-6553","authenticated-orcid":false,"given":"Maria Vittoria","family":"Cubellis","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Napoli \u201cFederico II\u201d, Complesso Universitario Monte Sant\u2019Angelo, Via Cinthia, 80126 Napoli, Italy"},{"name":"Institute of Biomolecular Chemistry ICB, CNR, Via Campi Flegrei 34, 80078 Pozzuoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-0156","authenticated-orcid":false,"given":"Giuseppina","family":"Andreotti","sequence":"additional","affiliation":[{"name":"Institute of Biomolecular Chemistry ICB, CNR, Via Campi Flegrei 34, 80078 Pozzuoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/978-0-387-46401-5_14","article-title":"Immunomodulation by curcumin","volume":"595","author":"Gautam","year":"2007","journal-title":"Adv. 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