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Degeneración axonal provocada por la activación retrógrada de la señalización somática pro-apoptótica

David J Simon¹, Jason Pitts¹, Nicholas T Hertz¹

¹Laboratory of Brain Development and Repair, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.

|February 23, 2016

Resumen

El cuerpo celular, no sólo los axones, controla activamente la degeneración de los axones. La pérdida de apoyo neurotrófico desencadena una señal retrógrada al cuerpo celular, iniciando la eliminación de axones.

Área de la Ciencia:

La neurociencia
Biología celular
Biología del desarrollo

Sus antecedentes:

El desarrollo de los axones sensoriales implica competencia por factores neurotróficos.
La privación local de neurotrofinas normalmente desencadena la degeneración del axón dependiente de la caspasa.
Los modelos existentes sugieren que la señalización de la degeneración del axón reside dentro del propio axón.

Objetivo del estudio:

Investigar el papel del cuerpo celular en la regulación de la degeneración de los axones tras la privación de neurotrofinas.
Para aclarar las vías de señalización involucradas en la degeneración del axón.

Principales métodos:

Investigó las vías de señalización en la degeneración del axón sensorial.
Centrado en el papel del cuerpo celular y la maquinaria apoptótica.

Principales resultados:

La degeneración axonal tras la privación local es controlada activamente por el cuerpo celular.
La pérdida de soporte trófico inicia la señalización retrógrada al cuerpo celular.
El cuerpo celular regula el Puma pro-apoptótico, que está confinado al cuerpo celular.
Puma supera la inhibición de Bcl-xL y Bcl-w, iniciando la señalización pro-degenerativa anterógrada.

Conclusiones:

El cuerpo celular es un guardián crítico para la degeneración del axón.
Una señal retrógrada de los axones privados activa las vías apoptóticas somáticas.
El cuerpo celular orquesta la eliminación de axones a través de factores anterógrados como Puma.

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