• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

阿尔茨海默病转基因小鼠模型中 IIa 类组蛋白去乙酰化酶表达的评估及体内表观遗传成像。

Evaluation of Class IIa Histone Deacetylases Expression and In Vivo Epigenetic Imaging in a Transgenic Mouse Model of Alzheimer's Disease.

机构信息

Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.

Molecular and Genetic Imaging Core/Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei 112, Taiwan.

出版信息

Int J Mol Sci. 2021 Aug 11;22(16):8633. doi: 10.3390/ijms22168633.

DOI:10.3390/ijms22168633
PMID:34445342
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8395513/
Abstract

Epigenetic regulation by histone deacetylase (HDAC) is associated with synaptic plasticity and memory formation, and its aberrant expression has been linked to cognitive disorders, including Alzheimer's disease (AD). This study aimed to investigate the role of class IIa HDAC expression in AD and monitor it in vivo using a novel radiotracer, 6-(tri-fluoroacetamido)-1-hexanoicanilide ([F]TFAHA). A human neural cell culture model with familial AD (FAD) mutations was established and used for in vitro assays. Positron emission tomography (PET) imaging with [F]TFAHA was performed in a 3xTg AD mouse model for in vivo evaluation. The results showed a significant increase in HDAC4 expression in response to amyloid-β (Aβ) deposition in the cell model. Moreover, treatment with an HDAC4 selective inhibitor significantly upregulated the expression of neuronal memory-/synaptic plasticity-related genes. In [F]TFAHA-PET imaging, whole brain or regional uptake was significantly higher in 3xTg AD mice compared with WT mice at 8 and 11 months of age. Our study demonstrated a correlation between class IIa HDACs and Aβs, the therapeutic benefit of a selective inhibitor, and the potential of using [F]TFAHA as an epigenetic radiotracer for AD, which might facilitate the development of AD-related neuroimaging approaches and therapies.

摘要

组蛋白去乙酰化酶（HDAC）的表观遗传调控与突触可塑性和记忆形成有关，其异常表达与认知障碍有关，包括阿尔茨海默病（AD）。本研究旨在研究 IIa 类 HDAC 表达在 AD 中的作用，并使用新型放射性示踪剂 6-（三氟乙酰氨基）-1-己酰苯胺([F]TFAHA) 进行体内监测。建立了具有家族性 AD (FAD) 突变的人神经细胞培养模型，并用于体外检测。用[F]TFAHA 对 3xTg AD 小鼠模型进行正电子发射断层扫描（PET）成像，进行体内评估。结果表明，细胞模型中 Aβ 沉积导致 HDAC4 表达显著增加。此外，用 HDAC4 选择性抑制剂处理可显著上调神经元记忆/突触可塑性相关基因的表达。在[F]TFAHA-PET 成像中，与 WT 小鼠相比，3xTg AD 小鼠在 8 个月和 11 个月时全脑或区域性摄取显著升高。我们的研究表明 IIa 类 HDAC 与 Aβ 之间存在相关性，选择性抑制剂具有治疗益处，并且 [F]TFAHA 可用作 AD 的表观遗传放射性示踪剂，这可能有助于开发 AD 相关的神经影像学方法和治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421d/8395513/9cedd778448a/ijms-22-08633-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421d/8395513/bfa3ae70dc69/ijms-22-08633-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421d/8395513/10c8a845330d/ijms-22-08633-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421d/8395513/9874aa713835/ijms-22-08633-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421d/8395513/847bc3c0a619/ijms-22-08633-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421d/8395513/9cedd778448a/ijms-22-08633-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421d/8395513/bfa3ae70dc69/ijms-22-08633-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421d/8395513/10c8a845330d/ijms-22-08633-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421d/8395513/9874aa713835/ijms-22-08633-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421d/8395513/847bc3c0a619/ijms-22-08633-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/421d/8395513/9cedd778448a/ijms-22-08633-g005.jpg

相似文献

1
Evaluation of Class IIa Histone Deacetylases Expression and In Vivo Epigenetic Imaging in a Transgenic Mouse Model of Alzheimer's Disease.阿尔茨海默病转基因小鼠模型中 IIa 类组蛋白去乙酰化酶表达的评估及体内表观遗传成像。
Int J Mol Sci. 2021 Aug 11;22(16):8633. doi: 10.3390/ijms22168633.
2
Novel Histone Deacetylase Class IIa Selective Substrate Radiotracers for PET Imaging of Epigenetic Regulation in the Brain.用于脑部表观遗传调控PET成像的新型IIa类组蛋白去乙酰化酶选择性底物放射性示踪剂
PLoS One. 2015 Aug 5;10(8):e0133512. doi: 10.1371/journal.pone.0133512. eCollection 2015.
3
Molecular imaging HDACs class IIa expression-activity and pharmacologic inhibition in intracerebral glioma models in rats using PET/CT/(MRI) with [F]TFAHA.使用 [F]TFAHA 的 PET/CT/（MRI）对大鼠颅内神经胶质瘤模型中的 HDACs Ⅱa 类分子成像表达-活性和药物抑制作用。
Sci Rep. 2019 Mar 5;9(1):3595. doi: 10.1038/s41598-019-40054-2.
4
Radionuclide labeling and evaluation of candidate radioligands for PET imaging of histone deacetylase in the brain.放射性核素标记及候选正电子发射断层扫描显像剂用于脑组蛋白去乙酰化酶的评价。
Bioorg Med Chem Lett. 2013 Dec 15;23(24):6700-5. doi: 10.1016/j.bmcl.2013.10.038. Epub 2013 Oct 30.
5
Evaluation of 6-([(18)F]fluoroacetamido)-1-hexanoicanilide for PET imaging of histone deacetylase in the baboon brain.6-([(18)F]氟乙酰氨基)-1-己酸苯胺用于狒狒脑组蛋白去乙酰化酶PET成像的评估。
Nucl Med Biol. 2009 Apr;36(3):247-58. doi: 10.1016/j.nucmedbio.2008.12.005.
6
Imaging epigenetic regulation by histone deacetylases in the brain using PET/MRI with ¹⁸F-FAHA.使用 ¹⁸F-FAHA 的 PET/MRI 对大脑中的组蛋白去乙酰化酶进行影像学的表观遗传调控。
Neuroimage. 2013 Jan 1;64:630-9. doi: 10.1016/j.neuroimage.2012.09.019. Epub 2012 Sep 17.
7
Spatial and temporal dynamics of HDACs class IIa following mild traumatic brain injury in adult rats.成年大鼠轻度创伤性脑损伤后IIa类组蛋白去乙酰化酶的时空动态变化
Mol Psychiatry. 2022 Mar;27(3):1683-1693. doi: 10.1038/s41380-021-01369-7. Epub 2022 Jan 14.
8
Longitudinal evaluation of a novel BChE PET tracer as an early biomarker in the brain of a mouse model for Alzheimer disease.新型丁酰胆碱酯酶 PET 示踪剂作为阿尔茨海默病小鼠模型早期生物标志物的纵向评估。
Theranostics. 2021 Apr 26;11(13):6542-6559. doi: 10.7150/thno.54589. eCollection 2021.
9
High-Contrast PET Imaging with [F]NT160, a Class-IIa Histone Deacetylase Probe for In Vivo Imaging of Epigenetic Machinery in the Central Nervous System.高对比度正电子发射断层扫描成像技术与[F]NT160，一种用于中枢神经系统中表观遗传学机制的体内成像的 IIa 类组蛋白去乙酰化酶探针。
J Med Chem. 2023 Apr 27;66(8):5611-5621. doi: 10.1021/acs.jmedchem.2c02064. Epub 2023 Apr 17.
10
[C]Martinostat PET analysis reveals reduced HDAC I availability in Alzheimer's disease.马丁司他汀正电子发射断层扫描分析显示阿尔茨海默病中组蛋白去乙酰化酶 I 的可用性降低。
Nat Commun. 2022 Jul 19;13(1):4171. doi: 10.1038/s41467-022-30653-5.

引用本文的文献

1
Epigenetics in Neurodegenerative Diseases.神经退行性疾病中的表观遗传学
Subcell Biochem. 2025;108:73-109. doi: 10.1007/978-3-031-75980-2_3.
2
Targeting epigenetic mechanisms in amyloid-β-mediated Alzheimer's pathophysiology: unveiling therapeutic potential.靶向淀粉样β蛋白介导的阿尔茨海默病病理生理过程中的表观遗传机制：揭示治疗潜力。
Neural Regen Res. 2025 Jan 1;20(1):54-66. doi: 10.4103/NRR.NRR-D-23-01827. Epub 2024 Mar 1.
3
Oxyresveratrol-β-cyclodextrin mitigates streptozotocin-induced Alzheimer's model cognitive impairment, histone deacetylase activity in rats: in silico & in vivo studies.

本文引用的文献

1
Role of Hypoxia Inducible Factor-1α in Alzheimer's Disease.缺氧诱导因子-1α 在阿尔茨海默病中的作用。
J Alzheimers Dis. 2021;80(3):949-961. doi: 10.3233/JAD-201448.
2
Epigenetic basis of Alzheimer disease.阿尔茨海默病的表观遗传基础。
World J Biol Chem. 2020 Sep 27;11(2):62-75. doi: 10.4331/wjbc.v11.i2.62.
3
Alzheimer's Patient Microglia Exhibit Enhanced Aging and Unique Transcriptional Activation.阿尔茨海默病患者小胶质细胞表现出增强的衰老和独特的转录激活。
原花青素-β-环糊精减轻链脲佐菌素诱导的大鼠阿尔茨海默病模型认知障碍，组蛋白去乙酰化酶活性：体内外研究。
Sci Rep. 2024 Apr 30;14(1):9897. doi: 10.1038/s41598-024-57188-7.
4
Relationship Between Reactive Astrocytes, by [F]SMBT-1 Imaging, with Amyloid-Beta, Tau, Glucose Metabolism, and TSPO in Mouse Models of Alzheimer's Disease.通过 [F]SMBT-1 成像研究阿尔茨海默病小鼠模型中反应性星形胶质细胞与淀粉样蛋白-β、tau、葡萄糖代谢和 TSPO 的关系。
Mol Neurobiol. 2024 Oct;61(10):8387-8401. doi: 10.1007/s12035-024-04106-7. Epub 2024 Mar 19.
5
Deciphering the roles of subcellular distribution and interactions involving the MEF2 binding region, the ankyrin repeat binding motif and the catalytic site of HDAC4 in Drosophila neuronal morphogenesis.解析 MEF2 结合区、锚蛋白重复结合基序和 HDAC4 催化位点在果蝇神经元形态发生中涉及的亚细胞分布和相互作用的作用。
BMC Biol. 2024 Jan 2;22(1):2. doi: 10.1186/s12915-023-01800-1.
6
Gut microbiota defined epigenomes of Alzheimer's and Parkinson's diseases reveal novel targets for therapy.肠道微生物群定义的阿尔茨海默病和帕金森病表观基因组揭示了新的治疗靶点。
Epigenomics. 2024 Jan;16(1):57-77. doi: 10.2217/epi-2023-0342. Epub 2023 Dec 13.
7
Enhancement of neural regeneration as a therapeutic strategy for Alzheimer's disease (Review).增强神经再生作为阿尔茨海默病的一种治疗策略（综述）。
Exp Ther Med. 2023 Aug 1;26(3):444. doi: 10.3892/etm.2023.12143. eCollection 2023 Sep.
8
Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.介绍用于胶质母细胞瘤成像和治疗的靶向组蛋白去乙酰化酶的放射性药物。
Pharmaceuticals (Basel). 2023 Feb 1;16(2):227. doi: 10.3390/ph16020227.
9
Epigenetic Changes and Chromatin Reorganization in Brain Function: Lessons from Fear Memory Ensemble and Alzheimer's Disease.脑功能中的表观遗传改变和染色质重排：来自恐惧记忆组合和阿尔茨海默病的教训。
Int J Mol Sci. 2022 Oct 11;23(20):12081. doi: 10.3390/ijms232012081.
10
A Class I HDAC Inhibitor Rescues Synaptic Damage and Neuron Loss in APP-Transfected Cells and APP/PS1 Mice through the GRIP1/AMPA Pathway.一种 I 类组蛋白去乙酰化酶抑制剂通过 GRIP1/AMPA 通路挽救 APP 转染细胞和 APP/PS1 小鼠的突触损伤和神经元丢失。
Molecules. 2022 Jun 29;27(13):4160. doi: 10.3390/molecules27134160.
Cell Rep. 2020 Jun 30;31(13):107843. doi: 10.1016/j.celrep.2020.107843.
4
Class IIa HDACs regulate learning and memory through dynamic experience-dependent repression of transcription.IIa 类组蛋白去乙酰化酶通过动态的经验依赖型转录抑制来调节学习和记忆。
Nat Commun. 2019 Aug 2;10(1):3469. doi: 10.1038/s41467-019-11409-0.
5
Epigenetic Modifications in Alzheimer's Neuropathology and Therapeutics.阿尔茨海默病神经病理学与治疗中的表观遗传修饰
Front Neurosci. 2019 May 10;13:476. doi: 10.3389/fnins.2019.00476. eCollection 2019.
6
Molecular imaging HDACs class IIa expression-activity and pharmacologic inhibition in intracerebral glioma models in rats using PET/CT/(MRI) with [F]TFAHA.使用 [F]TFAHA 的 PET/CT/（MRI）对大鼠颅内神经胶质瘤模型中的 HDACs Ⅱa 类分子成像表达-活性和药物抑制作用。
Sci Rep. 2019 Mar 5;9(1):3595. doi: 10.1038/s41598-019-40054-2.
7
Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes.iPSC 多巴胺神经元的单细胞测序重建疾病进展并鉴定出 HDAC4 为帕金森细胞表型的调节剂。
Cell Stem Cell. 2019 Jan 3;24(1):93-106.e6. doi: 10.1016/j.stem.2018.10.023. Epub 2018 Nov 29.
8
Alzheimer's disease.阿尔茨海默病
Nature. 2018 Jul;559(7715):S1. doi: 10.1038/d41586-018-05717-6.
9
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade.淀粉样β寡聚体假说：第三个十年的开端。
J Alzheimers Dis. 2018;64(s1):S567-S610. doi: 10.3233/JAD-179941.
10
Alzheimer's disease drug development pipeline: 2017.2017年阿尔茨海默病药物研发进展
Alzheimers Dement (N Y). 2017 May 24;3(3):367-384. doi: 10.1016/j.trci.2017.05.002. eCollection 2017 Sep.