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Una nueva vía regula la memoria y la plasticidad a través de SIRT1 y miR-134
Jun Gao1, Wen-Yuan Wang, Ying-Wei Mao
1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nature
|July 13, 2010
Resumen
La proteína SIRT1 regula la memoria y la plasticidad sináptica a través de una nueva vía de microARN. Este hallazgo revela un nuevo papel para SIRT1 en la función cerebral, distinto de sus funciones de supervivencia celular.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- SIRT1, un homólogo mamífero de la levadura Sir2, tiene funciones conocidas en la función cardíaca, la reparación del ADN y la estabilidad genómica.
- La evidencia emergente sugiere la participación de SIRT1 en la fisiología del cerebro y los trastornos neurológicos.
- El papel de SIRT1 en las funciones cerebrales de orden superior, como la cognición, sigue siendo en gran medida inexplorado.
Objetivo del estudio:
- Investigar el papel de SIRT1 en la plasticidad sináptica y la formación de la memoria.
- Para dilucidar los mecanismos moleculares subyacentes, centrándose particularmente en la regulación del microARN.
Principales métodos:
- Investigó los efectos de la activación y pérdida de función de SIRT1 en la plasticidad sináptica.
- Utilizó un mecanismo mediado por microARN que involucra a miR-134 y su regulación de la expresión de CREB y BDNF.
- Examinó la interacción entre SIRT1, YY1 y miR-134 en un complejo represor.
Principales resultados:
- La activación de SIRT1 aumentó, mientras que la deficiencia de SIRT1 deterioró la plasticidad sináptica y la formación de memoria.
- Estos efectos fueron mediados por el microARN específico del cerebro, miR-134, que regula post-transcripcionalmente la expresión de CREB.
- SIRT1 limita la expresión de miR-134 a través de un complejo represor que involucra a YY1; la deficiencia de SIRT1 conduce a un aumento de miR-134, una disminución de CREB y BDNF y una plasticidad deteriorada.
Conclusiones:
- SIRT1 juega un papel crucial en la modulación de la plasticidad sináptica y la formación de la memoria a través de una nueva vía dependiente del microARN.
- Este estudio identifica un nuevo mecanismo en el que SIRT1 regula la cognición a través de miR-134, CREB y BDNF, distinto de sus funciones de supervivencia celular.
- SIRT1 representa un objetivo terapéutico potencial para los trastornos del sistema nervioso central que afectan la función cognitiva.
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