Rationale for the development of 2-aminobenzamide histone deacetylase inhibitors as therapeutics for Friedreich ataxia.
J Child Neurol
; 27(9): 1164-73, 2012 Sep.
Article
en En
| MEDLINE
| ID: mdl-22764181
ABSTRACT
Numerous studies have pointed to histone deacetylase inhibitors as potential therapeutics for various neurodegenerative diseases, and clinical trials with several histone deacetylase inhibitors have been performed or are under way. However, histone deacetylase inhibitors tested to date either are highly cytotoxic or have very low specificities for different histone deacetylase enzymes. The authors' laboratories have identified a novel class of histone deacetylase inhibitors (2-aminobenzamides) that reverses heterochromatin-mediated silencing of the frataxin (FXN) gene in Friedreich ataxia. The authors have identified the histone deacetylase enzyme isotype target of these compounds and present evidence that compounds that target this enzyme selectively increase FXN expression from pathogenic alleles. Studies with model compounds show that these histone deacetylase inhibitors increase FXN messenger RNA levels in the brain in mouse models for Friedreich ataxia and relieve neurological symptoms observed in mouse models and support the notion that this class of molecules may serve as therapeutics for the human disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ataxia de Friedreich
/
Regulación de la Expresión Génica
/
Inhibidores de Histona Desacetilasas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Child Neurol
Asunto de la revista:
NEUROLOGIA
/
PEDIATRIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos