1. Degradation of Caytaxin Causes Learning and Memory Deficits via Activation of DAPK1 in Aging
- Author
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Lei Pei, Manfei Deng, Yu Guo, Xiao Ke, Youming Lu, Xiaoan Zhang, Zhuoze Wu, Hao Li, Henok Kessete Afewerky, and You Cai
- Subjects
Male ,0301 basic medicine ,Aging ,Small interfering RNA ,Neuroscience (miscellaneous) ,Hippocampus ,Nerve Tissue Proteins ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Memory ,Animals ,Gene silencing ,Gene Silencing ,Protein kinase A ,Neurons ,Memory Disorders ,Caspase 3 ,Chemistry ,Cell biology ,Enzyme Activation ,Mice, Inbred C57BL ,Death-Associated Protein Kinases ,030104 developmental biology ,Neurology ,Protein kinase domain ,Proteolysis ,030217 neurology & neurosurgery ,Degradation (telecommunications) - 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.
- Published
- 2018