Humanin and colivelin: Neuronal-death-suppressing peptides for Alzheimer's disease and amyotrophic lateral sclerosis
Humanin and colivelin: Neuronal-death-suppressing peptides for Alzheimer's disease and amyotrophic lateral sclerosis
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DOI：
10.1111/j.1527-3458.2006.00113.x
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发表时间：
2006-06-01
期刊：
影响因子：
--
通讯作者：
Nishimoto, Ikuo
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文献类型：
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作者：
Matsuoka, Masaaki;Hashimoto, Yuichi;Nishimoto, Ikuo
Humanin（HN）是一种由24个氨基酸组成的神经保护肽，最初发现于阿尔茨海默病（AD）尸检患者的枕叶中。HN通过与细胞膜上的特异性受体结合并触发Jak 2/STAT 3促存活途径来抑制神经元死亡。该途径的激活可能代表了AD的治疗方法。FIN还表现出对家族性肌萎缩侧索硬化症（ALS）相关突变型超氧化物歧化酶（SOD 1）毒性的神经保护活性。最近的研究证实，阿加-（C8 R）-HNG 17，一种FIN的17-氨基酸衍生物，作为神经保护剂的效力是HN的10（5）倍;在10皮摩尔和更高的体外浓度下，它完全抑制神经元死亡。此外，由活性依赖性神经营养因子（ADNF）C-末端融合到阿加-（C8 R）-HNG 17组成的26-氨基酸肽colivelin（CL）在体外在100-飞摩尔或更高浓度下提供完全的神经保护。使用小鼠AD和ALS模型的一系列实验进一步确立了HN衍生物（包括CL）在体内对抗这些疾病的功效。HN和CL可被视为AD或ALS中神经元死亡抑制治疗的候选药物。
Humanin (HN), a 24-amino-acid neuroprotective peptide, was originally found in the occipital lobe of an autopsied Alzheimer's disease (AD) patient. HN inhibits neuronal death by binding to its specific receptor on the cell membrane and triggering a Jak2/STAT3 prosurvival pathway. The activation of this pathway may represent a therapeutic approach to AD. FIN also exhibits neuroprotective activity against toxicity by familial amyotrophic lateral sclerosis (ALS)-related mutant superoxide dismutase (SOD1). Recent investigations established that AGA-(C8R)-HNG17, a 17-amno-acid derivative of FIN, is 10(5) times more potent as a neuroprotective than HN; at 10-picomolar and higher concentrations in vitro it completely suppresses neuronal death. Moreover, a 26-amino-acid peptide colivelin (CL), composed of activity-dependent neurotrophic factor (ADNF) C-terminally fused to AGA-(C8R)-HNG17, provides complete neuroprotection at 100-femtomolar or higher concentrations in vitro. A series of experiments using mouse AD and ALS models further established the efficacy of HN derivatives, including CL, against these diseases in vivo. HN and CL can be viewed as drug candidates for neuronal death suppression therapy in AD or ALS.