An examination of mutant superoxide dismutase-1 in modulating the mislocalization and aggregation of ALS-associated SOD1 in neurons and astrocytes

amyotrophic lateral sclerosis;cortical astrocyte;cortical neuron;G93A SOD1;mislocalization;apoptosis;611

자연과학대학 협동과정뇌과학전공 ;

University:서울대학교 대학원

关键词: amyotrophic lateral sclerosis;    cortical astrocyte;    cortical neuron;    G93A SOD1;    mislocalization;    apoptosis;    611;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/131205/1/000000021983.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

Mutations in superoxide dismutase-1 (SOD1) are associated with familial cases of amyotrophic lateral sclerosis (fALS). Owing to the similarities in sporadic and fALS forms, mutant SOD1 animal and cellular models are a useful tool to study the disease. In transgenic mice expressing either wild-type (wt) human SOD1 or mutant G93A-SOD1, we found that wtSOD1 was present in cytoplasm and in nuclei of cortical neurons and astrocytes, whereas mutant SOD1 was mainly cytoplasmic. Furthermore, mutant-type SOD1 can modulate the form of wtSOD1 in cortical neurons and astrocytes by transfection. Cells expressing G93A-SOD1 showed a higher DNA damage compared with those expressing wtSOD1, possibly because of a loss of nuclear protection. We show that mutant G93A-SOD1 modulates the mislocalization and aggregation in ALS-associated SOD1 in cortical neurons and astrocytes that through wtSOD1 transformed mutant form by transfected with G93A-SOD1. These findings implicate that soluble assembly of wt and mtSOD1 as possible mediators of toxic processes involved in initiating mislocalization and aggregation. Here, we provide evidence that cytoplasmic aggregates induce apoptosis in G93A-SOD1 mouse cortical neurons and astrocytes. Taken together, our results indicate that mtSOD1 is probably interacting with wtSOD1 via some mechanisms to produce the augmented toxicity and may influence the formation of aggregates and apoptosis.