细胞朊病毒蛋白和 Fyn 激酶介导的阿尔茨海默病淀粉样β诱导信号。
Amyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease.
机构信息
Cellular Neuroscience, Neurodegeneration and Repair Program, Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
出版信息
Prion. 2013 Jan-Feb;7(1):37-41. doi: 10.4161/pri.22212. Epub 2012 Sep 17.
Abstract
Alzheimer disease (AD) is the most prevalent cause of dementia. Amyloid-β (Aβ) oligomers are potent synaptotoxins thought to mediate AD-related phenotypes. Cellular prion protein (PrP(C)) has been identified as a high-affinity receptor for Aβ oligomers. Herein, we review the functional consequences of Aβ oligomer binding to PrP(C) on the neuronal surface. We highlight recent evidence that Fyn kinase mediates signal transduction downstream of the PrP(C)-Aβ oligomer complex. These studies suggest that PrP(C) has a central role in AD pathogenesis and may provide a target for therapeutic intervention in AD.
摘要
阿尔茨海默病（AD）是最常见的痴呆症病因。淀粉样β（Aβ）寡聚体是潜在的突触毒素，被认为介导 AD 相关表型。细胞朊蛋白（PrP(C)）已被确定为 Aβ 寡聚体的高亲和力受体。在此，我们综述了 Aβ 寡聚体与神经元表面 PrP(C)结合对其功能的影响。我们强调了最近的证据表明 Fyn 激酶介导了 PrP(C)-Aβ 寡聚体复合物下游的信号转导。这些研究表明，PrP(C)在 AD 发病机制中起核心作用，并可能为 AD 的治疗干预提供靶点。
相似文献
1
Amyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease.细胞朊病毒蛋白和 Fyn 激酶介导的阿尔茨海默病淀粉样β诱导信号。
Prion. 2013 Jan-Feb;7(1):37-41. doi: 10.4161/pri.22212. Epub 2012 Sep 17.
2
Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons.阿尔茨海默病淀粉样β寡聚体与突触后朊病毒蛋白结合，激活 Fyn，导致神经元损伤。
Nat Neurosci. 2012 Sep;15(9):1227-35. doi: 10.1038/nn.3178. Epub 2012 Jul 22.
3
Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer aβ oligomer bound to cellular prion protein.代谢型谷氨酸受体 5 是与细胞朊病毒蛋白结合的阿尔茨海默病 β 寡聚体的核心受体。
Neuron. 2013 Sep 4;79(5):887-902. doi: 10.1016/j.neuron.2013.06.036.
4
Cellular prion protein mediates the toxicity of beta-amyloid oligomers: implications for Alzheimer disease.细胞朊蛋白介导β-淀粉样寡聚体的毒性：对阿尔茨海默病的启示。
Arch Neurol. 2009 Nov;66(11):1325-8. doi: 10.1001/archneurol.2009.223.
5
Alzheimer's amyloid-β oligomers rescue cellular prion protein induced tau reduction via the Fyn pathway.阿尔茨海默病淀粉样-β寡聚体通过 Fyn 通路拯救细胞朊病毒蛋白诱导的 tau 减少。
ACS Chem Neurosci. 2013 Sep 18;4(9):1287-96. doi: 10.1021/cn400085q. Epub 2013 Jul 18.
6
The complex PrP(c)-Fyn couples human oligomeric Aβ with pathological tau changes in Alzheimer's disease.该复合物 PrP(c)-Fyn 将人类寡聚体 Aβ与阿尔茨海默病中的病理性 tau 变化偶联。
J Neurosci. 2012 Nov 21;32(47):16857-71a. doi: 10.1523/JNEUROSCI.1858-12.2012.
7
The Link of the Prion Protein with Ca Metabolism and ROS Production, and the Possible Implication in Aβ Toxicity.朊病毒蛋白与钙代谢和 ROS 产生的联系，以及其在 Aβ 毒性中的可能作用。
Int J Mol Sci. 2019 Sep 19;20(18):4640. doi: 10.3390/ijms20184640.
8
Cellular prion protein as a therapeutic target in Alzheimer's disease.细胞朊病毒蛋白作为阿尔茨海默病的治疗靶点。
J Alzheimers Dis. 2014;38(2):227-44. doi: 10.3233/JAD-130950.
9
Current Research Therapeutic Strategies for Alzheimer's Disease Treatment.阿尔茨海默病治疗的当前研究治疗策略
Neural Plast. 2016;2016:8501693. doi: 10.1155/2016/8501693. Epub 2016 Jan 3.
10
Systematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance.系统且标准化地比较报告的淀粉样β受体的充足性、亲和力和与阿尔茨海默病的相关性。
J Biol Chem. 2019 Apr 12;294(15):6042-6053. doi: 10.1074/jbc.RA118.006252. Epub 2019 Feb 20.
引用本文的文献
1
Cellular Prion Protein and Amyloid-β Oligomers in Alzheimer's Disease-Are There Connections?阿尔茨海默病中的细胞朊蛋白与β-淀粉样寡聚体——它们有关联吗？
Int J Mol Sci. 2025 Feb 27;26(5):2097. doi: 10.3390/ijms26052097.
2
Single-Nucleus Landscape of Glial Cells and Neurons in Alzheimer's Disease.阿尔茨海默病中神经胶质细胞和神经元的单核图谱
Mol Neurobiol. 2025 Mar;62(3):2695-2709. doi: 10.1007/s12035-024-04428-6. Epub 2024 Aug 17.
3
Fyn Kinase in Alzheimer's Disease: Unraveling Molecular Mechanisms and Therapeutic Implications.阿尔茨海默病中的Fyn激酶：揭示分子机制与治疗意义
Mol Neurobiol. 2025 Jan;62(1):643-660. doi: 10.1007/s12035-024-04286-2. Epub 2024 Jun 18.
4
primiReference: a reference for analysis of primary-microRNA expression in single-nucleus sequencing data.primiref：一种用于分析单细胞测序数据中初级-miRNA 表达的参考。
J Genet Genomics. 2023 Feb;50(2):108-121. doi: 10.1016/j.jgg.2022.10.003. Epub 2022 Nov 9.
5
Alzheimer's disease/dementia-associated brain pathology in aging DPP6-KO mice.衰老 DPP6-KO 小鼠的阿尔茨海默病/痴呆相关脑病理学。
Neurobiol Dis. 2022 Nov;174:105887. doi: 10.1016/j.nbd.2022.105887. Epub 2022 Oct 6.
6
Endosomal trafficking and related genetic underpinnings as a hub in Alzheimer's disease.内体运输及其相关遗传基础作为阿尔茨海默病的枢纽。
J Cell Physiol. 2022 Oct;237(10):3803-3815. doi: 10.1002/jcp.30864. Epub 2022 Aug 22.
7
Fyn Kinase Activity and Its Role in Neurodegenerative Disease Pathology: a Potential Universal Target?Fyn激酶活性及其在神经退行性疾病病理学中的作用：一个潜在的通用靶点？
Mol Neurobiol. 2021 Nov;58(11):5986-6005. doi: 10.1007/s12035-021-02518-3. Epub 2021 Aug 25.
8
Neurodegenerative Disease and the NLRP3 Inflammasome.神经退行性疾病与NLRP3炎性小体
Front Pharmacol. 2021 Mar 10;12:643254. doi: 10.3389/fphar.2021.643254. eCollection 2021.
9
Structural details of amyloid β oligomers in complex with human prion protein as revealed by solid-state MAS NMR spectroscopy.固态 MAS NMR 光谱揭示淀粉样β寡聚物与人朊病毒蛋白复合物的结构细节。
J Biol Chem. 2021 Jan-Jun;296:100499. doi: 10.1016/j.jbc.2021.100499. Epub 2021 Mar 3.
10
Understanding and exploiting interactions between cellular proteostasis pathways and infectious prion proteins for therapeutic benefit.理解和利用细胞蛋白质稳态途径与传染性朊病毒蛋白之间的相互作用，以获得治疗益处。
Open Biol. 2020 Nov;10(11):200282. doi: 10.1098/rsob.200282. Epub 2020 Nov 25.
本文引用的文献
1
Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons.阿尔茨海默病淀粉样β寡聚体与突触后朊病毒蛋白结合，激活 Fyn，导致神经元损伤。
Nat Neurosci. 2012 Sep;15(9):1227-35. doi: 10.1038/nn.3178. Epub 2012 Jul 22.
2
Aβ neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors.β 淀粉样蛋白神经毒性取决于铜离子、朊病毒蛋白和 N-甲基-D-天冬氨酸受体之间的相互作用。
Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1737-42. doi: 10.1073/pnas.1110789109. Epub 2012 Jan 17.
3
The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes.有毒的 Aβ 寡聚体与阿尔茨海默病：一个需要穿衣服的皇帝。
Nat Neurosci. 2012 Jan 29;15(3):349-57. doi: 10.1038/nn.3028.
4
Cellular prion protein is essential for oligomeric amyloid-β-induced neuronal cell death.细胞朊蛋白对于寡聚态淀粉样-β诱导的神经元细胞死亡是必需的。
Hum Mol Genet. 2012 Mar 1;21(5):1138-44. doi: 10.1093/hmg/ddr542. Epub 2011 Nov 18.
5
Ablation of cellular prion protein does not ameliorate abnormal neural network activity or cognitive dysfunction in the J20 line of human amyloid precursor protein transgenic mice.敲除细胞朊病毒蛋白不能改善人淀粉样前体蛋白转基因小鼠 J20 品系中异常的神经网络活动或认知功能障碍。
J Neurosci. 2011 Jul 20;31(29):10427-31. doi: 10.1523/JNEUROSCI.1459-11.2011.
6
Interaction between prion protein and toxic amyloid β assemblies can be therapeutically targeted at multiple sites.朊病毒蛋白与毒性淀粉样 β 聚合体之间的相互作用可以在多个靶点进行治疗性靶向。
Nat Commun. 2011 Jun 7;2:336. doi: 10.1038/ncomms1341.
7
Alzheimer's disease brain-derived amyloid-β-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein.阿尔茨海默病脑源性淀粉样蛋白-β在体内介导的 LTP 抑制可被针对细胞朊病毒蛋白的免疫靶向所预防。
J Neurosci. 2011 May 18;31(20):7259-63. doi: 10.1523/JNEUROSCI.6500-10.2011.
8
The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication.细胞朊病毒蛋白介导富含β-折叠构象的神经毒性信号，而不依赖于朊病毒复制。
EMBO J. 2011 May 18;30(10):2057-70. doi: 10.1038/emboj.2011.86. Epub 2011 Mar 25.
9
Amyloid-beta42 interacts mainly with insoluble prion protein in the Alzheimer brain.β淀粉样蛋白 42 主要与阿尔茨海默病脑中不溶性朊病毒蛋白相互作用。
J Biol Chem. 2011 Apr 29;286(17):15095-105. doi: 10.1074/jbc.M110.199356. Epub 2011 Mar 10.
10
Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an Alzheimer's disease model mouse.抗 PrPC 单克隆抗体输注作为一种新型治疗阿尔茨海默病模型小鼠认知缺陷的方法。
BMC Neurosci. 2010 Oct 14;11:130. doi: 10.1186/1471-2202-11-130.
Zotero 插件