Niikura Takako, Chiba Tomohiro, Aiso Sadakazu, Matsuoka Masaaki, Nishimoto Ikuo
Department of Pharmacology, KEIO University School of Medicine, Medical Research Building, Tokyo 160-8582, Japan.
Mol Neurobiol. 2004 Dec;30(3):327-40. doi: 10.1385/MN:30:3:327.
Humanin (HN) is a novel neuroprotective factor that consists of 24 amino acid residues. HN suppresses neuronal cell death caused by Alzheimer's disease (AD)-specific insults, including both amyloid-beta (betaAbeta) peptides and familial AD-causative genes. Cerebrovascular smooth muscle cells are also protected from Abeta toxicity by HN, suggesting that HN affects both neuronal and non-neuronal cells when they are exposed to AD-related cytotoxicity. HN peptide exerts a neuroprotective effect through the cell surface via putative receptor(s). HN activates a cellular signaling cascade that intervenes (at least) in activation of c-Jun N-terminal kinase. The highly selective effect of HN on AD-relevant cell death indicates that HN is promising for AD therapy. Additionally, a recent study showed that intracellularly overexpressed HN suppressed mitochondria-mediated apoptosis by inhibiting Bax activity.
人胰岛素（HN）是一种由24个氨基酸残基组成的新型神经保护因子。HN可抑制由阿尔茨海默病（AD）特异性损伤引起的神经元细胞死亡，这些损伤包括淀粉样β蛋白（β-淀粉样蛋白）肽和家族性AD致病基因。脑血管平滑肌细胞也受到HN的保护，免受β-淀粉样蛋白毒性的影响，这表明当神经元和非神经元细胞暴露于与AD相关的细胞毒性时，HN会对它们产生影响。HN肽通过假定的受体在细胞表面发挥神经保护作用。HN激活一种细胞信号级联反应，该反应（至少）干预c-Jun氨基末端激酶的激活。HN对与AD相关的细胞死亡具有高度选择性作用，这表明HN有望用于AD治疗。此外，最近的一项研究表明，细胞内过表达的HN通过抑制Bax活性来抑制线粒体介导的细胞凋亡。
