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SOCS3 deletion promotes optic nerve regeneration in vivo.
Smith, Patrice D; Sun, Fang; Park, Kevin Kyungsuk; Cai, Bin; Wang, Chen; Kuwako, Kenichiro; Martinez-Carrasco, Irene; Connolly, Lauren; He, Zhigang.
Afiliación
  • Smith PD; F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Neuron ; 64(5): 617-23, 2009 Dec 10.
Article en En | MEDLINE | ID: mdl-20005819
ABSTRACT
Axon regeneration failure accounts for permanent functional deficits following CNS injury in adult mammals. However, the underlying mechanisms remain elusive. In analyzing axon regeneration in different mutant mouse lines, we discovered that deletion of suppressor of cytokine signaling 3 (SOCS3) in adult retinal ganglion cells (RGCs) promotes robust regeneration of injured optic nerve axons. This regeneration-promoting effect is efficiently blocked in SOCS3-gp130 double-knockout mice, suggesting that SOCS3 deletion promotes axon regeneration via a gp130-dependent pathway. Consistently, a transient upregulation of ciliary neurotrophic factor (CNTF) was observed within the retina following optic nerve injury. Intravitreal application of CNTF further enhances axon regeneration from SOCS3-deleted RGCs. Together, our results suggest that compromised responsiveness to injury-induced growth factors in mature neurons contributes significantly to regeneration failure. Thus, developing strategies to modulate negative signaling regulators may be an efficient strategy of promoting axon regeneration after CNS injury.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos del Nervio Óptico / Proteínas Supresoras de la Señalización de Citocinas / Regeneración Nerviosa Tipo de estudio: Prognostic_studies Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2009 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Traumatismos del Nervio Óptico / Proteínas Supresoras de la Señalización de Citocinas / Regeneración Nerviosa Tipo de estudio: Prognostic_studies Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2009 Tipo del documento: Article País de afiliación: Estados Unidos