Secreted calmodulin-like skin protein ameliorates scopolamine-induced memory impairment
Secreted calmodulin-like skin protein ameliorates scopolamine-induced memory impairment
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DOI：
10.1097/wnr.0b013e328362d9fe
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发表时间：
2014-06-18
期刊：
影响因子：
1.7
通讯作者：
Matsuoka, Masaaki
中科院分区：
文献类型：
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作者：
Hayashi, Masaaki;Tajima, Hirohisa;Matsuoka, Masaaki
Humanin是一种短的生物活性肽，在多种细胞死亡模型中通过Humanin受体抑制细胞死亡。在体内，Humanin改善正常小鼠中毒蕈碱受体拮抗剂诱导的记忆障碍和阿尔茨海默病（AD）相关小鼠模型（包括表达家族性AD连锁基因的老年转基因小鼠）中的记忆障碍。最近，钙调素样皮肤蛋白（CLSP）已被证明是从皮肤组织分泌，包含一个区域最低限度地类似于Humanin的核心区域，并通过异源三聚体Humanin受体在体外细胞表面抑制AD相关的神经元死亡。由于CLSP比Humanin有效得多，并且通过血液循环穿过血脑屏障有效转运到中枢神经系统，因此CLSP被认为是一种生理激动剂，可结合异三聚体Humanin受体并触发Humanin诱导的信号中枢神经系统。然而，CLSP是否能像Humanin一样改善小鼠痴呆模型中的记忆障碍仍然是未知的。在这项研究中，我们表明，重组CLSP，脑室内或腹腔内给药，改善东莨菪碱诱导的痴呆小鼠。(C)2014年威科健康垂直酒吧利平科特威廉姆斯&威尔金斯。
Humanin, a short bioactive peptide, inhibits cell death in a variety of cell-based death models through Humanin receptors in vitro. In vivo, Humanin ameliorates both muscarinic receptor antagonist-induced memory impairment in normal mice and memory impairment in Alzheimer's disease (AD)-relevant mouse models including aged transgenic mice expressing a familial AD-linked gene. Recently, calmodulin-like skin protein (CLSP) has been shown to be secreted from skin tissues, contain a region minimally similar to the core region of Humanin, and inhibit AD-related neuronal death through the heterotrimeric Humanin receptor on the cell surface in vitro. As CLSP is much more potent than Humanin and efficiently transported through blood circulation across the blood-brain barrier to the central nervous system, CLSP is considered as a physiological agonist that binds to the heterotrimeric Humanin receptor and triggers the Humanin-induced signals in central nervous system. However, it remains unknown whether CLSP ameliorates memory impairment in mouse dementia models as Humanin does. In this study, we show that recombinant CLSP, administered intracerebroventricularly or intraperitoneally, ameliorates scopolamine-induced dementia in mice. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.