Degradation of Caytaxin Causes Learning and Memory Deficits via Activation of DAPK1 in Aging.

Abstract

Loss of memory is an inevitable clinic sign in aging, but its underlying mechanisms remain unclear. Here we show that death-associated protein kinase (DAPK1) is involved in the decays of learning and memory in aging via degradation of Caytaxin, a brain-specific member of BNIP-2. DAPK1 becomes activated in the hippocampus of mice during aging. Activation of DAPK1 is closely associated with degradation of Caytaxin protein. Silencing Caytaxin by the expression of small interfering RNA (siRNA) that targets specifically to Caytaxin in the hippocampus of adult mice impairs the learning and memory. Genetic inactivation of DAPK1 by deletion of DAPK1 kinase domain prevents the degradation of Caytaxin and protects against learning and memory declines. Thus, activation of DAPK1 impairs learning and memory by degrading Caytaxin during aging.