{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:19:38Z","timestamp":1792793978848,"version":"4.5.0"},"reference-count":99,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T00:00:00Z","timestamp":1578873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN 2015 2015JHLY35"],"award-info":[{"award-number":["PRIN 2015 2015JHLY35"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The term \u201cpharmacological chaperone\u201d was introduced 20 years ago. Since then the approach with this type of drug has been proposed for several diseases, lysosomal storage disorders representing the most popular targets. The hallmark of a pharmacological chaperone is its ability to bind a protein specifically and stabilize it. This property can be beneficial for curing diseases that are associated with protein mutants that are intrinsically active but unstable. The total activity of the affected proteins in the cell is lower than normal because they are cleared by the quality control system. Although most pharmacological chaperones are reversible competitive inhibitors or antagonists of their target proteins, the inhibitory activity is neither required nor desirable. This issue is well documented by specific examples among which those concerning Fabry disease. Direct specific binding is not the only mechanism by which small molecules can rescue mutant proteins in the cell. These drugs and the properly defined pharmacological chaperones can work together with different and possibly synergistic modes of action to revert a disease phenotype caused by an unstable protein.<\/jats:p>","DOI":"10.3390\/ijms21020489","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T04:05:51Z","timestamp":1578888351000},"page":"489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":126,"title":["Pharmacological Chaperones: A Therapeutic Approach for Diseases Caused by Destabilizing Missense Mutations"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8480-0501","authenticated-orcid":false,"given":"Ludovica","family":"Liguori","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"},{"name":"Istituto di Chimica Biomolecolare\u2013CNR, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3136-2138","authenticated-orcid":false,"given":"Maria","family":"Monticelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia, Universit\u00e0 Federico II, 80126 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3693-2515","authenticated-orcid":false,"given":"Mariateresa","family":"Allocca","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Universit\u00e0 degli Studi della Campania \u201cLuigi Vanvitelli\u201d, 81100 Caserta, Italy"},{"name":"Istituto di Chimica Biomolecolare\u2013CNR, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-183X","authenticated-orcid":false,"given":"Bruno","family":"Hay Mele","sequence":"additional","affiliation":[{"name":"Integrative Marine Ecology Department, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lukas","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht-Kossel\u201d, Department of Neurology, University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"},{"name":"Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6147-6553","authenticated-orcid":false,"given":"Maria Vittoria","family":"Cubellis","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare\u2013CNR, 80078 Pozzuoli, Italy"},{"name":"Dipartimento di Biologia, Universit\u00e0 Federico II, 80126 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-0156","authenticated-orcid":false,"given":"Giuseppina","family":"Andreotti","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare\u2013CNR, 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1080\/17512433.2018.1480367","article-title":"Pharmacoperone drugs: Targeting misfolded proteins causing lysosomal storage- ion channels-, and g protein-coupled receptors-associated conformational disorders","volume":"11","author":"Hou","year":"2018","journal-title":"Expert Rev. 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