Search

Your search keyword '"Lei, Pei"' showing total 5 results
Start Over Author "Lei, Pei" Publication Year Range Last 50 years Publisher society for neuroscience
5 results on '"Lei, Pei"'

1. Selective Degeneration of Entorhinal-CA1 Synapses in Alzheimer's Disease via Activation of DAPK1

Author

Ling-Qiang Zhu, Youming Lu, Xinyan Li, Wenting Chen, Dan Liu, Lei Pei, Qing Tian, Na Tang, Houze Zhu, Yangling Mu, Hao Li, and Shu Shu

Subjects
Male, 0301 basic medicine, Mice, Transgenic, Disease, Degeneration (medical), Motor Activity, Biology, Inhibitory postsynaptic potential, Activation, Metabolic, Mice, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Memory, Animals, Entorhinal Cortex, Humans, Direct pathway of movement, Maze Learning, Protein kinase A, CA1 Region, Hippocampal, Postural Balance, Research Articles, Death domain, Pyramidal Cells, General Neuroscience, Electrophysiological Phenomena, Death-Associated Protein Kinases, Parvalbumins, 030104 developmental biology, Synapses, Excitatory postsynaptic potential, biology.protein, Neuroscience, 030217 neurology & neurosurgery, Parvalbumin
Abstract

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 ECIIPNof AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN-CA1PVsynaptic loss and improves spatial learning and memory in AD mice. This study demonstrates that activation of DAPK1 in ECIIPNcontributes to a memory loss in AD and hence warrants a promising target for the treatment of AD.SIGNIFICANCE STATEMENTOur 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 ECIIPNof AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN-CA1PVsynaptic 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.

Published
2016

2. DAPK1–p53 Interaction Converges Necrotic and Apoptotic Pathways of Ischemic Neuronal Death

Author

You Shang, Huijuan Jin, Na Wei, Youming Lu, Lei Pei, Ling-Qiang Zhu, Xiaoxi Wang, Shan Wang, Yan Wu, Honglin Yan, and Chengye Yao

Subjects
Male, Necrosis, Apoptosis, Biology, Real-Time Polymerase Chain Reaction, Brain Ischemia, Cyclophilins, Mice, medicine, Animals, Immunoprecipitation, Cloning, Molecular, Luciferases, Protein kinase A, Gene, Cells, Cultured, Glutathione Transferase, bcl-2-Associated X Protein, Death domain, Neurons, General Neuroscience, Articles, Dependovirus, Cell Hypoxia, Cell biology, Mice, Inbred C57BL, Death-Associated Protein Kinases, Glucose, medicine.anatomical_structure, Mitochondrial matrix, Phosphorylation, Tumor Suppressor Protein p53, medicine.symptom, Nucleus, Cyclophilin D, Gene Deletion, Protein Binding, Signal Transduction
Abstract

Necrosis and apoptosis are two distinct types of mechanisms that mediate ischemic injury. But a signaling point of convergence between them has yet to be identified. Here, we show that activated death-associated protein kinase 1 (DAPK1), phosphorylates p53 at serine-23 (pS23) via a direct binding of DAPK1 death domain (DAPK1DD) to the DNA binding motif of p53 (p53DM). We uncover that thepS23acts as a functional version of p53 and mediates necrotic and apoptotic neuronal death; in the nucleus,pS23induces the expression of proapoptotic genes, such asBax, whereas in the mitochondrial matrix,pS23triggers necrosis via interaction with cyclophilin D (CypD) in cultured cortical neurons from mice. Deletion of DAPK1DD (DAPK1DDΔ) or application of Tat-p53DM that interrupts DAPK1–p53 interaction blocks these dual pathways ofpS23actions in mouse cortical neurons. Thus, the DAPK1–p53 interaction is a signaling point of convergence of necrotic and apoptotic pathways and is a desirable target for the treatment of ischemic insults.

Published
2014

3. Selective Degeneration of Entorhinal-CA1 Synapses in Alzheimer's Disease via Activation of DAPK1.

Author

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 (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. [ABSTRACT FROM AUTHOR]

Published
2016
Full Text
View/download PDF

4. DAPK1-p53 Interaction Converges Necrotic and Apoptotic Pathways of Ischemic Neuronal Death.

Author

Lei Pei, You Shang, Huijuan Jin, Shan Wang, Na Wei, Honglin Yan, Yan Wu, Chengye Yao, Xiaoxi Wang, Ling-Qiang Zhu, and Youming Lu

Subjects
*APOPTOSIS, *DRUG interactions, *NECROBIOTIC disorders, *TRANSIENT ischemic attack treatment, *NEUROPLASTICITY, *GENE expression, *LABORATORY mice
Abstract

Necrosis and apoptosis are two distinct types of mechanisms that mediate ischemic injury. But a signaling point of convergence between them has yet to be identified. Here, we show that activated death-associated protein kinase 1 (DAPK1), phosphorylates p53 at serine-23 (pS23) via a direct binding of DAPK1 death domain (DAPK1DD) to the DNA binding motif of p53 (p53DM). We uncover that the pS23 acts as a functional version of p53 and mediates necrotic and apoptotic neuronal death; in the nucleus, pS23 induces the expression of proapoptotic genes, such as Bax, whereas in the mitochondrial matrix, pS23 triggers necrosis via interaction with cyclophilin D (CypD) in cultured cortical neurons from mice. Deletion of DAPK1DD (DAPK1DDΔ) or application of Tat-p53DM that interrupts DAPK1-p53 interaction blocks these dual pathways of pS23 actions in mouse cortical neurons. Thus, the DAPK1-p53 interaction is a signaling point of convergence of necrotic and apoptotic pathways and is a desirable target for the treatment of ischemic insults. [ABSTRACT FROM AUTHOR]

Published
2014
Full Text
View/download PDF

5. EPAC Inhibition of SUR1 Receptor Increases Glutamate Release and Seizure Vulnerability.

Author

Kunpeng Zhao, Ruojian Wen, Xiaoxi Wang, Lei Pei, Ying Yang, You Shang, Bazan, Nicolas, Zhu, Ling-Qiang, Qing Tian, and Youming Lu

Subjects
SULFONYLUREAS, GLUTAMIC acid, AP-1 transcription factor, NEUROTRANSMITTERS, ADENOSINE triphosphate, GENE expression
Abstract

EPAC (Exchange Proteins Activated by cAMP) regulates glutamate transmitter release in the central neurons, but a role underlying this regulation has yet to be identified. Here we show that EPAC binds directly to the intracellular loop of an ATP-sensitive potassium (KATP) channel type-1 sulfonylurea receptor (SUR1) receptor consisting of amino acids 859 - 881 (SUR1 859-881). Ablation of EPAC or expression of SUR1 859-881, which intercepts EPAC-SUR1 binding, increases the open probability of KATP channels consisting of the Kir6.1 subunit and SUR1. Opening of KATP channels inhibits glutamate release and reduces seizure vulnerability in adult mice. Therefore, EPAC inter-action with SUR1 controls seizure susceptibility and possibly acts via regulation of glutamate release. [ABSTRACT FROM AUTHOR]

Published
2013
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results