卷曲裂隙改善中枢神经系统药物递送？
Frizzled fissure to improve central nervous system drug delivery?
机构信息
Department of Biomedical Sciences and Brain Barriers Research Center, University of Minnesota Medical School Duluth, Duluth, Minnesota, USA.
出版信息
J Cereb Blood Flow Metab. 2014 Aug;34(8):1257. doi: 10.1038/jcbfm.2014.98. Epub 2014 Jun 4.
Abstract
Delivery of therapeutics to the brain is challenging because of efflux pumps located in the vascular endothelium. A detailed analysis of Wnt signaling in a human brain endothelial cell line indicates that expression and function of P-glycoprotein, a major efflux transporter, is controlled by non-canonical Wnt signaling. Inhibition of this pathway leads to downregulation of P-glycoprotein and increased transcellular drug transport and reveals a potential strategy for improving drug delivery for treatment of neurologic diseases.
摘要
将治疗药物递送到大脑具有挑战性，因为血管内皮细胞中存在外排泵。对人脑血管内皮细胞系中 Wnt 信号的详细分析表明，主要外排转运蛋白 P-糖蛋白的表达和功能受非经典 Wnt 信号的控制。抑制该途径可导致 P-糖蛋白下调和跨细胞药物转运增加，并为改善神经疾病治疗的药物递送提供了一种潜在策略。
相似文献
1
Frizzled fissure to improve central nervous system drug delivery?卷曲裂隙改善中枢神经系统药物递送？
J Cereb Blood Flow Metab. 2014 Aug;34(8):1257. doi: 10.1038/jcbfm.2014.98. Epub 2014 Jun 4.
2
The cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cells.经典和非经典 Wnt 依赖性途径的串扰调节人血脑屏障细胞中 P-糖蛋白的表达。
J Cereb Blood Flow Metab. 2014 Aug;34(8):1258-69. doi: 10.1038/jcbfm.2014.100. Epub 2014 Jun 4.
3
Activation of beta-catenin signalling by GSK-3 inhibition increases p-glycoprotein expression in brain endothelial cells.通过抑制GSK-3激活β-连环蛋白信号传导可增加脑内皮细胞中P-糖蛋白的表达。
J Neurochem. 2008 Aug;106(4):1855-65. doi: 10.1111/j.1471-4159.2008.05537.x. Epub 2008 Jul 4.
4
Wnt3A Induces GSK-3β Phosphorylation and β-Catenin Accumulation Through RhoA/ROCK.Wnt3A通过RhoA/ROCK诱导GSK-3β磷酸化和β-连环蛋白积累。
J Cell Physiol. 2017 May;232(5):1104-1113. doi: 10.1002/jcp.25572. Epub 2016 Nov 20.
5
P-glycoprotein, breast cancer resistance protein, Organic Anion Transporter 3, and Transporting Peptide 1a4 during blood-brain barrier maturation: involvement of Wnt/β-catenin and endothelin-1 signaling.血脑屏障成熟过程中的 P-糖蛋白、乳腺癌耐药蛋白、有机阴离子转运蛋白 3 和转运肽 1a4：Wnt/β-连环蛋白和内皮素-1 信号的参与。
Mol Pharm. 2013 May 6;10(5):1566-80. doi: 10.1021/mp300334r. Epub 2012 Oct 12.
6
Temozolomide downregulates P-glycoprotein expression in glioblastoma stem cells by interfering with the Wnt3a/glycogen synthase-3 kinase/β-catenin pathway.替莫唑胺通过干扰 Wnt3a/糖原合酶激酶/β-连环蛋白通路下调胶质母细胞瘤干细胞中的 P-糖蛋白表达。
Neuro Oncol. 2013 Nov;15(11):1502-17. doi: 10.1093/neuonc/not104. Epub 2013 Jul 28.
7
Galectin-3 silencing inhibits epirubicin-induced ATP binding cassette transporters and activates the mitochondrial apoptosis pathway via β-catenin/GSK-3β modulation in colorectal carcinoma.沉默半乳糖凝集素-3 通过β-连环蛋白/GSK-3β 调节抑制表阿霉素诱导的 ABC 转运蛋白并激活结直肠癌细胞中的线粒体凋亡途径。
PLoS One. 2013 Nov 26;8(11):e82478. doi: 10.1371/journal.pone.0082478. eCollection 2013.
8
β-Catenin Is Required for Endothelial Cyp1b1 Regulation Influencing Metabolic Barrier Function.β-连环蛋白是内皮细胞Cyp1b1调节影响代谢屏障功能所必需的。
J Neurosci. 2016 Aug 24;36(34):8921-35. doi: 10.1523/JNEUROSCI.0148-16.2016.
9
Knockdown of the Wnt receptor Frizzled-1 (FZD1) reduces MDR1/P-glycoprotein expression in multidrug resistant leukemic cells and inhibits leukemic cell proliferation.敲低Wnt受体卷曲蛋白1（FZD1）可降低多药耐药白血病细胞中MDR1/P-糖蛋白的表达，并抑制白血病细胞增殖。
Leuk Res. 2018 Apr;67:99-108. doi: 10.1016/j.leukres.2018.01.020. Epub 2018 Jan 31.
10
CD82 inhibits canonical Wnt signalling by controlling the cellular distribution of β-catenin in carcinoma cells.CD82 通过控制β-连环蛋白在癌细胞中的细胞分布来抑制经典 Wnt 信号通路。
Int J Oncol. 2012 Dec;41(6):2021-8. doi: 10.3892/ijo.2012.1671. Epub 2012 Oct 17.
引用本文的文献
1
Suppressing Wnt signaling of the blood‒tumor barrier to intensify drug delivery and inhibit lipogenesis of brain metastases.抑制血脑肿瘤屏障的Wnt信号传导以增强药物递送并抑制脑转移瘤的脂肪生成。
Acta Pharm Sin B. 2024 Jun;14(6):2716-2731. doi: 10.1016/j.apsb.2024.03.024. Epub 2024 Mar 21.
本文引用的文献
1
The cross-talk between canonical and non-canonical Wnt-dependent pathways regulates P-glycoprotein expression in human blood-brain barrier cells.经典和非经典 Wnt 依赖性途径的串扰调节人血脑屏障细胞中 P-糖蛋白的表达。
J Cereb Blood Flow Metab. 2014 Aug;34(8):1258-69. doi: 10.1038/jcbfm.2014.100. Epub 2014 Jun 4.
2
Drug transport across the blood-brain barrier.药物穿越血脑屏障的转运。
J Cereb Blood Flow Metab. 2012 Nov;32(11):1959-72. doi: 10.1038/jcbfm.2012.126. Epub 2012 Aug 29.
3
Delivery of molecularly targeted therapy to malignant glioma, a disease of the whole brain.将分子靶向治疗递送至恶性脑胶质瘤，一种全脑疾病。
Expert Rev Mol Med. 2011 May 13;13:e17. doi: 10.1017/S1462399411001888.
4
Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors.人血脑屏障转运体和受体的定量靶向绝对蛋白质组学。
J Neurochem. 2011 Apr;117(2):333-45. doi: 10.1111/j.1471-4159.2011.07208.x. Epub 2011 Feb 25.
5
Wnt/beta-catenin signaling: components, mechanisms, and diseases.Wnt/β-连环蛋白信号传导：组成部分、机制及相关疾病
Dev Cell. 2009 Jul;17(1):9-26. doi: 10.1016/j.devcel.2009.06.016.
6
Rho GTPase activity modulates Wnt3a/beta-catenin signaling.Rho GTP酶活性调节Wnt3a/β-连环蛋白信号通路。
Cell Signal. 2009 Nov;21(11):1559-68. doi: 10.1016/j.cellsig.2009.05.010. Epub 2009 May 29.
7
Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs.小鼠多药耐药蛋白1a（mdr1a）P-糖蛋白基因的破坏导致血脑屏障缺陷，并增加对药物的敏感性。
Cell. 1994 May 20;77(4):491-502. doi: 10.1016/0092-8674(94)90212-7.
Zotero 插件