RT Journal Article
SR Electronic
T1 Selective Degeneration of Entorhinal-CA1 Synapses in Alzheimer's Disease via Activation of DAPK1
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10843
OP 10852
DO 10.1523/JNEUROSCI.2258-16.2016
VO 36
IS 42
A1 Shu Shu
A1 Houze Zhu
A1 Na Tang
A1 Wenting Chen
A1 Xinyan Li
A1 Hao Li
A1 Lei Pei
A1 Dan Liu
A1 Yangling Mu
A1 Qing Tian
A1 Ling-Qiang Zhu
A1 Youming Lu
YR 2016
UL http://www.jneurosci.org/content/36/42/10843.abstract
AB Excitatory pyramidal neurons in the entorhinal cortical layer II region (ECIIPN) 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.SIGNIFICANCE STATEMENT Our recent study reported that excitatory pyramidal neurons in the entorhinal cortical layer II region (ECIIPN) target to CA1 parvalbumin-type inhibitory neurons (CA1PV) at a direct pathway and are one of the most vulnerable brain cells that are selectively degenerated in the early stage of Alzheimer's disease (AD). Our present study shows 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 the early stage of AD. These data not only demonstrate a crucial molecular event for synaptic degeneration but also provide a therapeutic target for the treatment of AD.