{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T08:28:26Z","timestamp":1762504106051},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,9,17]],"date-time":"2016-09-17T00:00:00Z","timestamp":1474070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Tuscany Region Bando Salute 2009","award":["158"],"award-info":[{"award-number":["158"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>Krabbe's disease (KD) is a degenerative lysosomal storage disease resulting from deficiency of \u03b2\u2010galactocerebrosidase activity. Over 100 mutations are known to cause the disease, and these usually occur in compound heterozygote patterns. In affected patients, nonsense mutations leading to a nonfunctional enzyme are often found associated with other mutations. The twitcher mouse is a naturally occurring model of KD, containing in \u03b2\u2010galactocerebrosidase a premature stop codon, W339X. Recent studies have shown that selected compounds may induce the ribosomal bypass of premature stop codons without affecting the normal termination codons. The rescue of \u03b2\u2010galactocerebrosidase activity induced by treatment with premature termination codon (PTC) 124, a well\u2010characterized compound known to induce ribosomal read\u2010through, was investigated on oligodendrocytes prepared from twitcher mice and on human fibroblasts from patients bearing nonsense mutations. The effectiveness of the nonsense\u2010mediated mRNA decay (NMD) inhibitor 1 (NMDI1), a newly identified inhibitor of NMD, was also tested. Incubation of these cell lines with PTC124 and NMDI1 increased the levels of mRNA and rescued galactocerebrosidase enzymatic activity in a dose\u2010dependent manner. The low but sustained expression of \u03b2\u2010galactocerebrosidase in oligodendrocytes was sufficient to improve the morphology of the differentiated cells. Our in vitro approach provides the basis for further investigation of ribosomal read\u2010through as an alternative therapeutic strategy to ameliorate the quality of life in selected KD patients. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23790","type":"journal-article","created":{"date-parts":[[2016,9,17]],"date-time":"2016-09-17T11:22:31Z","timestamp":1474111351000},"page":"1273-1283","source":"Crossref","is-referenced-by-count":5,"title":["Suppression of galactocerebrosidase premature termination codon and rescue of galactocerebrosidase activity in twitcher cells"],"prefix":"10.1002","volume":"94","author":[{"given":"Alice","family":"Luddi","sequence":"first","affiliation":[{"name":"Department of Molecular and Developmental Medicine Siena University Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Crifasi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Medicine Siena 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