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.