Calmodulin-like skin protein protects against spatial learning impairment in a mouse model of Alzheimer disease
Calmodulin-like skin protein protects against spatial learning impairment in a mouse model of Alzheimer disease
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DOI：
10.1111/jnc.14258
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发表时间：
2018-01-01
影响因子：
4.7
通讯作者：
Matsuoka, Masaaki
中科院分区：
文献类型：
--
作者：
Kusakari, Shinya;Nawa, Mikiro;Matsuoka, Masaaki
Humanin和钙调素样皮肤蛋白（CLSP）通过异源三聚体Humanin受体抑制阿尔茨海默病（AD）相关的神经元细胞死亡。已表明CLSP是体内异源三聚体人蛋白受体的中心激动剂。为了研究CLSP在体内AD发病机制中的作用，我们制备了小鼠CLSP-1转基因小鼠，将其与AD模型小鼠APPswe/PSEN 1dE 9小鼠杂交，并检查CLSP过表达对AD小鼠模型病理表型的影响。我们发现小鼠CLSP-1基因的过度表达减弱了APPswe/PSEN 1dE 9小鼠的空间学习障碍、突触前标记物突触素的丢失和STAT 3的失活。另一方面，CLSP过表达不影响A β、可溶性A β寡聚体或神经胶质增生的水平。这些结果表明，CLSP介导的记忆障碍和突触丢失的衰减以A β非依赖性方式发生。本研究结果对进一步认识AD的发病机制和发展AD的治疗具有一定的参考价值。
Humanin and calmodulin-like skin protein (CLSP) inhibits Alzheimer disease (AD)-related neuronal cell death via the heterotrimeric humanin receptor in vitro. It has been suggested that CLSP is a central agonist of the heterotrimeric humanin receptor in vivo. To investigate the role of CLSP in the AD pathogenesis in vivo, we generated mouse CLSP-1 transgenic mice, crossed them with the APPswe/PSEN1dE9 mice, a model mouse of AD, and examined the effect of CLSP overexpression on the pathological phenotype of the AD mouse model. We found that over-expression of the mouse CLSP-1 gene attenuated spatial learning impairment, the loss of a presynaptic marker synaptophysin, and the inactivation of STAT3 in the APPswe/PSEN1dE9 mice. On the other hand, CLSP over-expression did not affect levels of A beta, soluble A beta oligomers, or gliosis. These results suggest that the CLSP-mediated attenuation of memory impairment and synaptic loss occurs in an A beta-independent manner. The results of this study may serve as a hint to the better understanding of the AD pathogenesis and the development of AD therapy.