http://www.cnr.it/ontology/cnr/individuo/prodotto/ID281098
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
- Pagina fine
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
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- 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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