Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I
Departments of Pharmacology and Neurosciences, KEIO University School of Medicine, 160-8582 Tokyo, Japan.
Proc Natl Acad Sci U S A. 2001 May 22;98(11):6336-41. doi: 10.1073/pnas.101133498.
Through functional expression screening, we identified a gene, designated Humanin (HN) cDNA, which encodes a short polypeptide and abolishes death of neuronal cells caused by multiple different types of familial Alzheimer's disease genes and by Abeta amyloid, without effect on death by Q79 or superoxide dismutase-1 mutants. Transfected HN cDNA was transcribed to the corresponding polypeptide and then was secreted into the cultured medium. The rescue action clearly depended on the primary structure of HN. This polypeptide would serve as a molecular clue for the development of new therapeutics for Alzheimer's disease targeting neuroprotection.
通过功能表达筛选,我们鉴定出一个基因,命名为人胰岛素(HN)cDNA,它编码一种短多肽,可消除由多种不同类型的家族性阿尔茨海默病基因和β淀粉样蛋白引起的神经元细胞死亡,而对Q79或超氧化物歧化酶-1突变体引起的细胞死亡没有影响。转染的HN cDNA转录为相应的多肽,然后分泌到培养基中。这种挽救作用显然取决于HN的一级结构。这种多肽将作为开发针对神经保护的阿尔茨海默病新疗法的分子线索。