Mechanisms and therapeutic challenges in autism spectrum disorders: insights from Rett syndrome.
Curr Opin Neurol
; 26(2): 154-9, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23449173
ABSTRACT
PURPOSE OF REVIEW A major challenge for understanding neurodevelopmental disorders, including autism spectrum disorders (ASDs), is to advance the findings from gene discovery to an exposition of neurobiological mechanisms that underlie these disorders and subsequently translate this knowledge into mechanism-based therapeutics. A promising way to proceed is revealed by the recent studies of rare subsets of ASDs. In this review, we summarize the latest advances in the mechanisms and emerging therapeutics for a rare single-gene ASD, Rett syndrome. RECENT FINDINGS:
Rett syndrome is caused by mutations in the gene coding for methyl CpG-binding protein 2 (MeCP2). Although MeCP2 has diverse functions, examination of MeCP2 mutant mice suggests the hypothesis that MeCP2 deficiency leads to aberrant maturation and maintenance of synapses and circuits in multiple brain systems. Some of the deficits arise from alterations in specific intracellular pathways such as the PI3K/Akt signaling pathway. These abnormalities can be at least partially rescued in MeCP2 mutant mice by treatment with therapeutic agents.SUMMARY:
Mechanism-based therapeutics are emerging for single-gene neurodevelopmental disorders such as Rett syndrome. Given the complexity of MeCP2 function, future directions include combination therapeutics that target multiple molecules and pathways. Such approaches will likely be applicable to other ASDs as well.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Rett
/
Transtornos Globais do Desenvolvimento Infantil
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Proteína 2 de Ligação a Metil-CpG
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Child
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article