J Korean Neurol Assoc > Volume 20(3); 2002 > Article

Journal of the Korean Neurological Association 2002;20(3): 273-278.

"가족성 근위축성 측삭 경화증 연관성 Cu, Zn-superoxide dismutase 변이가 운동신경세포의 분화에 미치는 영향"

박경석 , 김현정 김남희 김만호 박성호 박웅양 김용식 이병란 차중익 채양석 이광우

인제대학교 서울백병원 신경과학교실,서울특별시립 보라매병원 신경과

"Effect of Familial Amyotrophic Lateral Sclerosis-associated Cu, Zn-superox-ide Dismutase Mutation on Neural Differentiation in Motor Neuronal Cells"

Kyung-Seok Park, M.D.

Department of Neurology, Inje University Seoul Paik Hospital and Seoul Municipal Boramae Hospital

Abstract

"Background : Mutations in the human Cu,Zn-superoxide dismutase(SOD1) gene have been identified in some cases of familial amyotrophic lateral sclerosis(ALS). The aim of this study is to delineate the effect of the SOD1 mutation on neural differentiation, and to investigate the mechanism of neuronal death. Methods : We studied motorneuron-neurob-lastoma hybrid cells(VSC 4.1) expressing wild type or mutant SOD1(G93A, A4V) during differentiation by dibutyryl cAMP and aphidicolin. Results : Mutant cells(G93A) revealed a decreased viability compared with the control cells, mainly in the early stage ofdifferentiation. The release of cytochrome c and increased nuclear fragmentation were observed. However, cell death was not protected by nonselective caspase inhibitor(z-VAD-fmk), but by the antioxi-dant( Trolox). Conclusions : The results suggest that oxidative stress may be the main mechanism of neuronal death, particularly in the early stage of differentiation.Key Words : Familial amyotrophic lateral sclerosis(ALS), Neural differentiation, Mutations in Cu, Zn-superoxide dis-mutase( SOD1), Oxidative stress, Neuronal death"