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下调阿尔茨海默病中升高的 Wnt 拮抗剂 Dickkopf-3，可恢复疾病模型小鼠的突触完整性和记忆。

Downregulation of Dickkopf-3, a Wnt antagonist elevated in Alzheimer's disease, restores synapse integrity and memory in a disease mouse model.

机构信息

Department of Cell and Developmental Biology, Division of Biosciences, University College London, London, United Kingdom.

Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom.

出版信息

Elife. 2024 Jan 29;12:RP89453. doi: 10.7554/eLife.89453.

DOI:10.7554/eLife.89453
PMID:38285009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10945611/
Abstract

Increasing evidence supports a role for deficient Wnt signaling in Alzheimer's disease (AD). Studies reveal that the secreted Wnt antagonist Dickkopf-3 (DKK3) colocalizes to amyloid plaques in AD patients. Here, we investigate the contribution of DKK3 to synapse integrity in healthy and AD brains. Our findings show that DKK3 expression is upregulated in the brains of AD subjects and that DKK3 protein levels increase at early stages in the disease. In hAPP-J20 and hAPP mouse AD models, extracellular DKK3 levels are increased and DKK3 accumulates at dystrophic neuronal processes around plaques. Functionally, DKK3 triggers the loss of excitatory synapses through blockade of the Wnt/GSK3β signaling with a concomitant increase in inhibitory synapses via activation of the Wnt/JNK pathway. In contrast, DKK3 knockdown restores synapse number and memory in hAPP-J20 mice. Collectively, our findings identify DKK3 as a novel driver of synaptic defects and memory impairment in AD.

摘要

越来越多的证据表明，Wnt 信号通路缺陷在阿尔茨海默病（AD）中起作用。研究表明，分泌型 Wnt 拮抗剂 Dickkopf-3（DKK3）与 AD 患者的淀粉样斑块共定位。在这里，我们研究了 DKK3 对健康和 AD 大脑中突触完整性的贡献。我们的研究结果表明，DKK3 在 AD 患者的大脑中表达上调，并且在疾病的早期阶段 DKK3 蛋白水平增加。在 hAPP-J20 和 hAPP 小鼠 AD 模型中，细胞外 DKK3 水平增加，DKK3 聚集在斑块周围的神经突中。功能上，DKK3 通过阻断 Wnt/GSK3β 信号通路触发兴奋性突触的丧失，同时通过激活 Wnt/JNK 通路增加抑制性突触。相比之下，DKK3 敲低可恢复 hAPP-J20 小鼠的突触数量和记忆。总的来说，我们的研究结果表明 DKK3 是 AD 中突触缺陷和记忆损伤的新驱动因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/f0ef85b4349c/elife-89453-fig7-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/bdfa62af94a4/elife-89453-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/cb99ab78c6e6/elife-89453-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/a8d4b0e9cecf/elife-89453-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/cadf807b05b3/elife-89453-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/6cd43aeb8baa/elife-89453-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/a4c973094656/elife-89453-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/0764be74c949/elife-89453-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/8a74bdb3ffcb/elife-89453-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/938160043bbf/elife-89453-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/b191cf765dac/elife-89453-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/bb9f4d132279/elife-89453-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/7078c931769d/elife-89453-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/faebed9b9fac/elife-89453-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/f0ef85b4349c/elife-89453-fig7-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/bdfa62af94a4/elife-89453-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/cb99ab78c6e6/elife-89453-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/a8d4b0e9cecf/elife-89453-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/cadf807b05b3/elife-89453-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/6cd43aeb8baa/elife-89453-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/a4c973094656/elife-89453-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/0764be74c949/elife-89453-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/8a74bdb3ffcb/elife-89453-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/938160043bbf/elife-89453-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/b191cf765dac/elife-89453-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/bb9f4d132279/elife-89453-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/7078c931769d/elife-89453-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/faebed9b9fac/elife-89453-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e53/10945611/f0ef85b4349c/elife-89453-fig7-figsupp1.jpg

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本文引用的文献

[1]
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EMBO Rep. 2023-8-3

[2]
A genetic variant of the Wnt receptor LRP6 accelerates synapse degeneration during aging and in Alzheimer's disease.

Sci Adv. 2023-1-13

[3]
Macrophage NFATC2 mediates angiogenic signaling during mycobacterial infection.

Cell Rep. 2022-12-13

[4]
Epigenetic repression of Wnt receptors in AD: a role for Sirtuin2-induced H4K16ac deacetylation of Frizzled1 and Frizzled7 promoters.

Mol Psychiatry. 2022-7

[5]
Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.

Nat Neurosci. 2022-2

[6]
Disruption of ER-mitochondria tethering and signalling in C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia.

Aging Cell. 2022-2

[7]
Striatal Synapse Degeneration and Dysfunction Are Reversed by Reactivation of Wnt Signaling.

Front Synaptic Neurosci. 2021-6-3

[8]
Clathrin light chain diversity regulates membrane deformation in vitro and synaptic vesicle formation in vivo.

Proc Natl Acad Sci U S A. 2020-9-9

[9]
Comparative profiling of the synaptic proteome from Alzheimer's disease patients with focus on the APOE genotype.

Acta Neuropathol Commun. 2019-12-20

[10]
Regional protein expression in human Alzheimer's brain correlates with disease severity.

Commun Biol. 2019-2-4

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