{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T05:52:59Z","timestamp":1774504379172,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Fabry disease is an X-linked multisystemic disorder caused by the impairment of lysosomal \u03b1-Galactosidase A, which leads to the progressive accumulation of glycosphingolipids and to defective lysosomal metabolism. Currently, Fabry disease is treated by enzyme replacement therapy or the orally administrated pharmacological chaperone Migalastat. Both therapeutic strategies present limitations, since enzyme replacement therapy has shown low half-life and bioavailability, while Migalastat is only approved for patients with specific mutations. The aim of this work was to assess the efficacy of PBX galactose analogues to stabilize \u03b1-Galactosidase A and therefore evaluate their potential use in Fabry patients with mutations that are not amenable to the treatment with Migalastat. We demonstrated that PBX compounds are safe and effective concerning stabilization of \u03b1-Galactosidase A in relevant cellular models of the disease, as assessed by enzymatic activity measurements, molecular modelling, and cell viability assays. This experimental evidence suggests that PBX compounds are promising candidates for the treatment of Fabry disease caused by mutations which affect the folding of \u03b1-Galactosidase A, even for GLA variants that are not amenable to the treatment with Migalastat.<\/jats:p>","DOI":"10.3390\/biom11121856","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T08:17:58Z","timestamp":1639124278000},"page":"1856","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The New Pharmacological Chaperones PBXs Increase \u03b1-Galactosidase A Activity in Fabry Disease Cellular Models"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9985-9063","authenticated-orcid":false,"given":"Pedro","family":"Besada","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Universidade de Vigo, 36310 Vigo, Spain"},{"name":"BIOILS Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Gallardo-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Rare Diseases and Pediatric Medicine Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"P\u00e9rez-M\u00e1rquez","sequence":"additional","affiliation":[{"name":"Rare Diseases and Pediatric Medicine Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc\u00eda","family":"Pati\u00f1o-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Rare Diseases and Pediatric Medicine Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6435-4543","authenticated-orcid":false,"given":"Sergio","family":"Pantano","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecular Simulations, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4955-9844","authenticated-orcid":false,"given":"Carlos","family":"Silva-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Universidade de Vigo, 36310 Vigo, Spain"},{"name":"BIOILS Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4377-3604","authenticated-orcid":false,"given":"Carmen","family":"Ter\u00e1n","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Universidade de Vigo, 36310 Vigo, Spain"},{"name":"BIOILS Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Ar\u00e9valo-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University Hospital of A Coru\u00f1a (CHUAC-SERGS), 15006 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurora","family":"Ruz-Zafra","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital de la Serran\u00eda, Ronda, 29400 Malaga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juli\u00e1n","family":"Fern\u00e1ndez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Rare Diseases and Pediatric Medicine Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1098-3376","authenticated-orcid":false,"given":"Saida","family":"Ortolano","sequence":"additional","affiliation":[{"name":"Rare Diseases and Pediatric Medicine Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36312 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/gim.2016.55","article-title":"Is it Fabry disease?","volume":"18","author":"Schiffmann","year":"2016","journal-title":"Genet. 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