Defective neurite outgrowth in aphidicolin/cAMP-induced motor neurons expressing mutant Cu/Zn superoxide dismutase.
Int J Dev Neurosci
; 20(6): 521-6, 2002 Oct.
Article
em En
| MEDLINE
| ID: mdl-12392756
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron involvement. Mutations in the human Cu/Zn superoxide dismutase (SOD1) gene are found in some cases of familial ALS. Many studies have reported SOD1 mutation-related neurodegeneration. However, whether or not a mutant SOD1 affects neural development has not been demonstrated. We developed motor neuron-neuroblastoma hybrid cells that expressed a mutant (G93A) or the wild type (WT) SOD1. Cells were differentiated by dibutyryl cAMP and aphidicolin. The mutant showed a defect in neurite outgrowth and had decreased viability. Cytochrome c released and nuclear fragmentation were observed. Western blot analysis showed that the amount of neurofilament and microtubule associated proteins-2 (MAP-2) decreased during differentiation. These results suggest that the defect in neurite outgrowth of mutant SOD1 cells is a cytoskeletal defect and is associated with neuronal death.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Superóxido Dismutase
/
Diferenciação Celular
/
Sobrevivência Celular
/
Neuritos
/
Esclerose Lateral Amiotrófica
/
Neurônios Motores
/
Mutação
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article