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Alzheimer's disease;; Amyloid-beta peptide;; Calhm1;; Insulin-degrading enzyme;; Ion channel;; Secretion
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Full-Text Articles in Medicine and Health Sciences
Calhm1 Ion Channel Elicits Amyloid-Beta Clearance By Insulin-Degrading Enzyme In Cell Lines And In Vivo In The Mouse Brain, V. Vingtdeux, P. Chandakkar, H. Zhao, L. Blanc, S. Ruiz, P. Marambaud
Calhm1 Ion Channel Elicits Amyloid-Beta Clearance By Insulin-Degrading Enzyme In Cell Lines And In Vivo In The Mouse Brain, V. Vingtdeux, P. Chandakkar, H. Zhao, L. Blanc, S. Ruiz, P. Marambaud
Journal Articles
Alzheimer's disease is characterized by amyloid-beta (Abeta) peptide accumulation in the brain. CALHM1, a cell-surface Ca(2+) channel expressed in brain neurons, has anti-amyloidogenic properties in cell cultures. Here, we show that CALHM1 controls Abeta levels in vivo in the mouse brain through a previously unrecognized mechanism of regulation of Abeta clearance. Using pharmacological and genetic approaches in cell lines, we found that CALHM1 ion permeability and extracellular Ca(2+) were required for the Abeta-lowering effect of CALHM1. Abeta level reduction by CALHM1 could be explained by an increase in extracellular Abeta degradation by insulin-degrading enzyme (IDE), extracellular secretion of which was …