1. Selective Degeneration of Entorhinal-CA1 Synapses in Alzheimer's Disease via Activation of DAPK1.
- Author
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Shu Shu, Houze Zhu, Na Tang, Wenting Chen, Xinyan Li, Hao Li, Lei Pei, Dan Liu, Yangling Mu, Qing Tian, Ling-Qiang Zhu, and Youming Lu
- Subjects
ALZHEIMER'S disease treatment ,BRAIN degeneration ,ENTORHINAL cortex ,SYNAPSES ,PROTEIN kinases ,LABORATORY mice - Abstract
Excitatory pyramidal neurons in the entorhinal cortical layer II region (ECII
PN ) form functional excitatory synapses with CA1 parvalbumin inhibitory neurons (CA1PV ) and undergo selective degeneration in the early stages of Alzheimer's disease (AD). Here, we show that death-associated protein kinase 1 (DAPK1) is selectively activated in ECIIPN of AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN -CA1PV synaptic loss and improves spatial learning and memory in AD mice. This study demonstrates that activation of DAPK1 in ECIIPN contributes to a memory loss in AD and hence warrants a promising target for the treatment of AD. [ABSTRACT FROM AUTHOR]- Published
- 2016
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