http://www.cnr.it/ontology/cnr/individuo/prodotto/ID312690
Pharmacological chaperones to cure genetic diseases: development of drugs and identification of new targets (Progetti)
- Type
- Label
- Pharmacological chaperones to cure genetic diseases: development of drugs and identification of new targets (Progetti) (literal)
- Anno
- 2012-01-01T00:00:00+01:00 (literal)
- Alternative label
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- G. Andreotti, M.V.Cubellis (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Istituto di chimica Biomolecolare-Pozzuoli-CNR
Dipartimento Biologia Strutturale e Funzionale, UNINA (literal)
- Titolo
- Pharmacological chaperones to cure genetic diseases: development of drugs and identification of new targets (literal)
- Abstract
- A promising strategy for the treatment of some genetic diseases has been proposed recently: it exploits small molecules
which can be administered orally, can reach 'difficult' tissues such as the brain and have low cost. They act as life jackets or
chaperones for proteins that, become unstable and are degraded upon mutation, although they retain the essential residues
needed for activity. The same mutant proteins are able to comply their duty if they are given the chance to survive long
enough and to get to the site where they are needed. The approach is getting known as pharmacological chaperone (PC)
therapy and despite its novelty, it has produced a few drugs which are already in clinical trials. Fabry disease is a disorders
which can benefit from PC therapy. A large variability of genotypes and phenotypes is observed and only a fraction of
missense mutations respond to PC therapy. The effects of missense mutations and hence their responsiveness to drugs,
depends on the site where they occur in the protein. We can learn from Fabry disease which are the molecular requisites and
the limits to employ PC therapy. Moreover we can develop for this pathology novel drugs with higher potency and selectivity.
Serendipity led to the discovery of PCs for the treatment of a few genetic diseases, most notably lysosomal storage
diseases. Yet this approach can be successfully employed in a variety of cases. A large scale analysis of mutations
responsible of monogenetic diseases was carried out producing many potential targets for PCs. We decided to start with
congenital disorder of glycosylation, type Ia, a syndrome with no cure at present. We have already demonstrated that a
mutation frequently encountered in this pathology can be rescued by using small chemical chaperones (literal)
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