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

Type
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, Universit√† 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)
Editore
Prodotto di
Autore CNR
Insieme di parole chiave

Incoming links:


Autore CNR di
Prodotto
Editore di
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
Insieme di parole chiave di
data.CNR.it