Therapeutic targeting of misfolding and conformational change in α1-antitrypsin deficiency.
Future Med Chem
; 6(9): 1047-65, 2014 Jun.
Article
en En
| MEDLINE
| ID: mdl-25068987
ABSTRACT
Misfolding and conformational diseases are increasing in prominence and prevalence. Both misfolding and 'postfolding' conformational mechanisms can contribute to pathogenesis and can coexist. The different contexts of folding and native state behavior may have implications for the development of therapeutic strategies. α1-antitrypsin deficiency illustrates how these issues can be addressed with therapeutic approaches to rescue folding, ameliorate downstream consequences of aberrant polymerization and/or maintain physiological function. Small-molecule strategies have successfully targeted structural features of the native conformer. Recent developments include the capability to follow solution behavior of α1-antitrypsin in the context of disease mutations and interactions with drug-like compounds. Moreover, preclinical studies in cells and organisms support the potential of manipulating cellular response repertoires to process misfolded and polymer states.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Alfa 1-Antitripsina
/
Pliegue de Proteína
/
Deficiencia de alfa 1-Antitripsina
/
Bibliotecas de Moléculas Pequeñas
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Future Med Chem
Año:
2014
Tipo del documento:
Article
País de afiliación:
Reino Unido