Mechanisms of Neuronal Alternative Splicing and Strategies for Therapeutic Interventions.
J Neurosci
; 39(42): 8193-8199, 2019 10 16.
Article
em En
| MEDLINE
| ID: mdl-31619487
ABSTRACT
Many cellular and physiological processes are coordinated by regulatory networks that produce a remarkable complexity of transcript isoforms. In the mammalian nervous system, alternative pre-mRNA splicing generates functionally distinct isoforms that play key roles in normal physiology, supporting development, plasticity, complex behaviors, and cognition. Neuronal splicing programs controlled by RNA-binding proteins, are influenced by chromatin modifications and can exhibit neuronal subtype specificity. As highlighted in recent publications, aberrant alternative splicing is a major contributor to disease phenotypes. Therefore, understanding the underlying mechanisms of alternative splicing regulation and identifying functional splicing isoforms with critical phenotypic roles are expected to provide a comprehensive resource for therapeutic development, as illuminated by recent successful interventions of spinal muscular atrophy. Here, we discuss the latest progress in the study of the emerging complexity of alternative splicing mechanisms in neurons, and how these findings inform new therapies to correct and control splicing defects.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Atrofia Muscular Espinal
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Processamento Alternativo
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Transtorno do Espectro Autista
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Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2019
Tipo de documento:
Article