Does wild-type Cu/Zn-superoxide dismutase have pathogenic roles in amyotrophic lateral sclerosis?

• 作者: Yoshiaki Furukawa Eichi Tokuda
• 来源期刊: 转化神经变性病(英文)
• 学科: 医学
• 关键词: Amyotrophic lateral sclerosis Cu/Zn-superoxide dismutase Protein misfolding
• 年，卷（期）: zhsjbxbyw_2020,（3）
• 页码范围: 421-436
• 页数: 16页
• 分类号: R74

摘要

Amyotrophic lateral sclerosis(ALS)is characterized by adult-onset progressive degeneration of upper and lower motor neurons.Increasing numbers of genes are found to be associated with ALS;among those,the first identified gene,SOD1 coding a Cu/Zn-superoxide dismutase protein(SOD1),has been regarded as the gold standard in the research on a pathomechanism of ALS.Abnormal accumulation of misfolded SOD1 in affected spinal motor neurons has been established as a pathological hallmark of ALS caused by mutations in SOD1(SOD1-ALS).Nonetheless,the involvement of wild-type SOD1 remains quite controversial in the pathology of ALS with no SOD1 mutations(non-SOD1 ALS),which occupies more than 90%of total ALS cases.In vitro studies have revealed post-translationally controlled misfolding and aggregation of wild-type as well as of mutant SOD1 proteins;therefore,SOD1 proteins could be a therapeutic target not only in SOD1-ALS but also in more prevailing cases,non-SOD1 ALS.In order to search for evidence on misfolding and aggregation of wild-type SOD1 in vivo,we reviewed pathological studies using mouse models and patients and then summarized arguments for and against possible involvement of wild-type SOD1 in non-SOD1 ALS as well as in SOD1-ALS.