An Jae Jin, Lee Yeom Pyo, Kim So Young, Lee Sun Hwa, Kim Dae Won, Lee Min Jung, Jeong Min Seop, Jang Sang Ho, Kang Jung Hoon, Kwon Hyeok Yil, Kang Tae-Cheon, Won Moo Ho, Cho Sung-Woo, Kwon Oh-Shin, Lee Kil Soo, Park Jinseu, Eum Won Sik, Choi Soo Young
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
Mol Cells. 2008 Feb 29;25(1):55-63.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the selective death of motor neurons. Mutations in the SOD1 gene are responsible for a familial form of ALS (FALS). Although many studies suggest that mutant SOD1 proteins are cytotoxic, the mechanism is not fully understood. To investigate the role of mutant SOD1 in FALS, human SOD1 genes were fused with a PEP-1 peptide in a bacterial expression vector to produce in-frame PEP-1-SOD fusion proteins (wild type and mutants). The expressed and purified PEP-1-SOD fusion proteins were efficiently transduced into neuronal cells. Neurones harboring the A4V, G93A, G85R, and D90A mutants of PEP-1-SOD were more vulnerable to oxidative stress induced by paraquat than those harboring wild-type proteins. Moreover, neurones harboring the mutant SOD proteins had lower heat shock protein (Hsp) expression levels than those harboring wild-type SOD. The effects of the transduced SOD1 fusion proteins may provide an explanation for the association of SOD1 with FALS, and Hsps could be candidate agents for the treatment of ALS.
肌萎缩侧索硬化症（ALS）是一种进行性神经退行性疾病，其特征是运动神经元选择性死亡。SOD1基因的突变导致家族性ALS（FALS）。尽管许多研究表明突变型SOD1蛋白具有细胞毒性，但其机制尚未完全明确。为了研究突变型SOD1在FALS中的作用，将人SOD1基因与PEP-1肽在细菌表达载体中融合，以产生读码框内的PEP-1-SOD融合蛋白（野生型和突变型）。表达并纯化的PEP-1-SOD融合蛋白被有效地转导到神经元细胞中。携带PEP-1-SOD的A4V、G93A、G85R和D90A突变体的神经元比携带野生型蛋白的神经元更容易受到百草枯诱导的氧化应激的影响。此外，携带突变型SOD蛋白的神经元的热休克蛋白（Hsp）表达水平低于携带野生型SOD的神经元。转导的SOD1融合蛋白的作用可能为SOD1与FALS的关联提供解释，并且Hsps可能是治疗ALS的候选药物。
