Calmodulin-like skin protein protects against spatial learning impairment in a mouse model of Alzheimer disease.

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 overexpression 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 overexpression did not affect levels of Aβ, soluble Aβ oligomers, or gliosis. These results suggest that the CLSP-mediated attenuation of memory impairment and synaptic loss occurs in an Aβ-independent manner. The results of the current study may serve as a hint to the better understanding of the AD pathogenesis and the development of AD therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Citation

Shinya Kusakari, Mikiro Nawa, Katsuko Sudo, Masaaki Matsuoka. Calmodulin-like skin protein protects against spatial learning impairment in a mouse model of Alzheimer disease. Journal of neurochemistry. 2017 Nov 21

PMID: 29164613

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