A thermodynamic assay to test pharmacological chaperones for Fabry disease (Articolo in rivista)

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Label
  • A thermodynamic assay to test pharmacological chaperones for Fabry disease (Articolo in rivista) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.bbagen.2013.12.018 (literal)
Alternative label
  • Giuseppina Andreotti a,?, Valentina Citro b, Antonella Correra b,c, Maria Vittoria Cubellis c,d,?? (2014)
    A thermodynamic assay to test pharmacological chaperones for Fabry disease
    in Biochimica et biophysica acta. G, General subjects (Print); Elsevier BV, Amsterdam (Paesi Bassi)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Giuseppina Andreotti a,?, Valentina Citro b, Antonella Correra b,c, Maria Vittoria Cubellis c,d,?? (literal)
Pagina inizio
  • 1214 (literal)
Pagina fine
  • 1224 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 1840 (literal)
Rivista
Note
  • Scopus (literal)
  • PubMed (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • a Istituto di Chimica Biomolecolare, CNR, Pozzuoli, Italy b Istituto di Genetica e Biofisica 'A. Buzzati Traverso,' CNR, Napoli, Italy c Dipartimento di Biologia, Università Federico II, Napoli, Italy d Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy (literal)
Titolo
  • A thermodynamic assay to test pharmacological chaperones for Fabry disease (literal)
Abstract
  • Background: Themajority of the disease-causingmutations affect protein stability, but not functional sites and are amenable, in principle, to be treated with pharmacological chaperones. These drugs enhance the thermodynamic stability of their targets. Fabry disease, a disorder caused by mutations in the gene encoding lysosomal alpha-galactosidase, represents an excellentmodel systemto develop experimental protocols to test the efficiency of such drugs. Methods: The stability of lysosomal alpha-galactosidase under different conditions was studied by urea-induced unfolding followed by limited proteolysis andWestern blotting. Results:Wemeasured the concentration of urea needed to obtain half-maximal unfolding because this parameter represents an objective indicator of protein stability. Conclusions: Urea-induced unfolding is a versatile technique that can be adapted to cell extracts containing tiny amounts of wild-type or mutant proteins. It allows testing of protein stability as a function of pH, in the presence or in the absence of drugs. Results are not influenced by the method used to express the protein in transfected cells. General significance: Scarce and dispersed populations pose a problem for the clinical trial of drugs for rare diseases. This is particularly true for pharmacological chaperones that must be tested on each mutation associated with a given disease. Diverse in vitro tests are needed.We used a method based on chemically induced unfolding as a tool to assess whether a particular Fabry mutation is responsive to pharmacological chaperones, but, by no means is our protocol limited to this disease. (literal)
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