帕金森病的可诱导α-突触核蛋白表达神经元细胞系模型 1.
An Inducible Alpha-Synuclein Expressing Neuronal Cell Line Model for Parkinson's Disease1.
机构信息
Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX, USA.
Centre for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, City of Knowledge, Republic of Panama.
出版信息
J Alzheimers Dis. 2018;66(2):453-460. doi: 10.3233/JAD-180610.
Abstract
Altered expression of α-synuclein is linked to Parkinson's disease (PD). A major challenge to explore how the increased α-synuclein affect neurotoxicity is the lack of a suitable human neuronal cell model that mimics this scenario. Its expression in neural precursors affects their differentiation process, in addition to the neuronal adaptability and variability in maintaining a constant level of expression across passages. Here, we describe an SH-SY5Y line harboring Tet-ON SNCA cDNA cassette that allows for induction of controlled α-synuclein expression after neuronal differentiation, which can be an important tool for PD research.
摘要
α-突触核蛋白的表达改变与帕金森病（PD）有关。探索增加的α-突触核蛋白如何影响神经毒性的主要挑战是缺乏合适的人类神经元细胞模型来模拟这种情况。它在神经前体细胞中的表达会影响它们的分化过程，此外，还会影响神经元的适应性和在整个传代过程中保持恒定表达水平的可变性。在这里，我们描述了一种含有 Tet-ON SNCA cDNA 盒的 SH-SY5Y 系，该系允许在神经元分化后诱导可控的α-突触核蛋白表达，这可能是 PD 研究的重要工具。
相似文献
1
An Inducible Alpha-Synuclein Expressing Neuronal Cell Line Model for Parkinson's Disease1.帕金森病的可诱导α-突触核蛋白表达神经元细胞系模型 1.
J Alzheimers Dis. 2018;66(2):453-460. doi: 10.3233/JAD-180610.
2
Impairment of mitochondria dynamics by human A53T α-synuclein and rescue by NAP (davunetide) in a cell model for Parkinson's disease.人A53T α-突触核蛋白对线粒体动力学的损害及帕金森病细胞模型中NAP（达武奈肽）的挽救作用
Exp Brain Res. 2017 Mar;235(3):731-742. doi: 10.1007/s00221-016-4836-9. Epub 2016 Nov 19.
3
Chromatin-Bound Oxidized α-Synuclein Causes Strand Breaks in Neuronal Genomes in in vitro Models of Parkinson's Disease.在帕金森病的体外模型中，染色质结合的氧化α-突触核蛋白导致神经元基因组中的链断裂。
J Alzheimers Dis. 2017;60(s1):S133-S150. doi: 10.3233/JAD-170342.
4
Expression of the Parkinson's Disease-Associated Gene Alpha-Synuclein is Regulated by the Neuronal Cell Fate Determinant TRIM32.帕金森病相关基因 Alpha-Synuclein 的表达受神经元细胞命运决定因子 TRIM32 的调节。
Mol Neurobiol. 2017 Aug;54(6):4257-4270. doi: 10.1007/s12035-016-9989-9. Epub 2016 Jun 23.
5
Rotenone down-regulates HSPA8/hsc70 chaperone protein in vitro: A new possible toxic mechanism contributing to Parkinson's disease.鱼藤酮在体外下调HSPA8/hsc70伴侣蛋白：一种导致帕金森病的新的可能毒性机制。
Neurotoxicology. 2016 May;54:161-169. doi: 10.1016/j.neuro.2016.04.018. Epub 2016 Apr 28.
6
Changes in sphingomyelin level affect alpha-synuclein and ABCA5 expression.鞘磷脂水平的变化会影响α-突触核蛋白和 ABCA5 的表达。
J Parkinsons Dis. 2012;2(1):41-6. doi: 10.3233/JPD-2012-11059.
7
Levodopa (L-DOPA) attenuates endoplasmic reticulum stress response and cell death signaling through DRD2 in SH-SY5Y neuronal cells under α-synuclein-induced toxicity.在α-突触核蛋白诱导的毒性作用下，左旋多巴（L-DOPA）通过SH-SY5Y神经细胞中的DRD2减轻内质网应激反应和细胞死亡信号。
Neuroscience. 2017 Sep 1;358:336-348. doi: 10.1016/j.neuroscience.2017.06.060. Epub 2017 Jul 4.
8
Suppression of MAPK attenuates neuronal cell death induced by activated glia-conditioned medium in alpha-synuclein overexpressing SH-SY5Y cells.在过表达α-突触核蛋白的SH-SY5Y细胞中，抑制丝裂原活化蛋白激酶（MAPK）可减轻由活化的神经胶质细胞条件培养基诱导的神经元细胞死亡。
J Neuroinflammation. 2015 Oct 26;12:193. doi: 10.1186/s12974-015-0412-7.
9
Microarray expression analysis of human dopaminergic neuroblastoma cells after RNA interference of SNCA--a key player in the pathogenesis of Parkinson's disease.帕金森病发病机制中的关键因子α-突触核蛋白（SNCA）RNA干扰后人多巴胺能神经母细胞瘤细胞的基因芯片表达分析
Brain Res. 2009 Feb 23;1256:19-33. doi: 10.1016/j.brainres.2008.12.020. Epub 2008 Dec 24.
10
Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival.细胞产生的α-突触核蛋白通过外泌体以钙离子依赖的方式分泌，并影响神经元的存活。
J Neurosci. 2010 May 19;30(20):6838-51. doi: 10.1523/JNEUROSCI.5699-09.2010.
引用本文的文献
1
Mitochondria-targeted oligomeric α-synuclein induces TOM40 degradation and mitochondrial dysfunction in Parkinson's disease and parkinsonism-dementia of Guam.线粒体靶向的寡聚α-突触核蛋白在帕金森病和关岛帕金森病痴呆中诱导TOM40降解和线粒体功能障碍。
Cell Death Dis. 2024 Dec 18;15(12):914. doi: 10.1038/s41419-024-07258-5.
2
Targeting protein aggregation using a cocoa-bean shell extract to reduce α-synuclein toxicity in models of Parkinson's disease.利用可可豆壳提取物靶向蛋白质聚集以降低帕金森病模型中α-突触核蛋白的毒性。
Curr Res Food Sci. 2024 Oct 24;9:100888. doi: 10.1016/j.crfs.2024.100888. eCollection 2024.
3
Mitochondria-Targeted Oligomeric α-Synuclein Induces TOM40 Degradation and Mitochondrial Dysfunction in Parkinson's Disease and Parkinsonism-Dementia of Guam.线粒体靶向的寡聚α-突触核蛋白在帕金森病和关岛帕金森痴呆综合征中诱导TOM40降解及线粒体功能障碍。
Res Sq. 2024 Feb 21:rs.3.rs-3970470. doi: 10.21203/rs.3.rs-3970470/v1.
4
α-Synuclein-dependent increases in PIP5K1γ drive inositol signaling to promote neurotoxicity.α-突触核蛋白依赖性 PIP5K1γ 的增加驱动肌醇信号转导促进神经毒性。
Cell Rep. 2023 Oct 31;42(10):113244. doi: 10.1016/j.celrep.2023.113244. Epub 2023 Oct 14.
5
α-Syn overexpression, NRF2 suppression, and enhanced ferroptosis create a vicious cycle of neuronal loss in Parkinson's disease.α-突触核蛋白过度表达、NRF2 抑制和增强的铁死亡导致帕金森病神经元丢失的恶性循环。
Free Radic Biol Med. 2022 Nov 1;192:130-140. doi: 10.1016/j.freeradbiomed.2022.09.015. Epub 2022 Sep 21.
6
Focused Ultrasound-Induced Blood-Brain Barrier Opening Enhanced α-Synuclein Expression in Mice for Modeling Parkinson's Disease.聚焦超声诱导的血脑屏障开放增强了用于帕金森病建模的小鼠中α-突触核蛋白的表达。
Pharmaceutics. 2022 Feb 18;14(2):444. doi: 10.3390/pharmaceutics14020444.
7
Live-Cell Assays for Cell Stress Responses Reveal New Patterns of Cell Signaling Caused by Mutations in Rhodopsin, α-Synuclein and TDP-43.用于细胞应激反应的活细胞分析揭示了视紫红质、α-突触核蛋白和TDP-43突变引起的细胞信号传导新模式。
Front Cell Neurosci. 2019 Dec 18;13:535. doi: 10.3389/fncel.2019.00535. eCollection 2019.
8
A multi-faceted genotoxic network of alpha-synuclein in the nucleus and mitochondria of dopaminergic neurons in Parkinson's disease: Emerging concepts and challenges.帕金森病多巴胺能神经元细胞核和线粒体中 alpha-突触核蛋白的多方面遗传毒性网络：新兴概念和挑战。
Prog Neurobiol. 2020 Feb;185:101729. doi: 10.1016/j.pneurobio.2019.101729. Epub 2019 Dec 18.
9
Amyotrophic lateral sclerosis-associated TDP-43 mutation Q331K prevents nuclear translocation of XRCC4-DNA ligase 4 complex and is linked to genome damage-mediated neuronal apoptosis.肌萎缩侧索硬化相关 TDP-43 突变 Q331K 阻止 XRCC4-DNA 连接酶 4 复合物的核易位，并与基因组损伤介导的神经元凋亡有关。
Hum Mol Genet. 2019 Aug 1;28(15):2459-2476. doi: 10.1093/hmg/ddz062. Epub 2019 Apr 1.
本文引用的文献
1
Modeling Parkinson's disease pathology by combination of fibril seeds and α-synuclein overexpression in the rat brain.通过在大鼠脑内共表达纤维种子和α-突触核蛋白来模拟帕金森病病理学。
Proc Natl Acad Sci U S A. 2017 Sep 26;114(39):E8284-E8293. doi: 10.1073/pnas.1710442114. Epub 2017 Sep 12.
2
Chromatin-Bound Oxidized α-Synuclein Causes Strand Breaks in Neuronal Genomes in in vitro Models of Parkinson's Disease.在帕金森病的体外模型中，染色质结合的氧化α-突触核蛋白导致神经元基因组中的链断裂。
J Alzheimers Dis. 2017;60(s1):S133-S150. doi: 10.3233/JAD-170342.
3
α-Synuclein fibril-induced inclusion spread in rats and mice correlates with dopaminergic Neurodegeneration.α-突触核蛋白原纤维诱导的包涵体在大鼠和小鼠中的扩散与多巴胺能神经退行性变相关。
Neurobiol Dis. 2017 Sep;105:84-98. doi: 10.1016/j.nbd.2017.05.014. Epub 2017 May 30.
4
α-Synuclein-Based Animal Models of Parkinson's Disease: Challenges and Opportunities in a New Era.基于α-突触核蛋白的帕金森病动物模型：新时代的挑战与机遇。
Trends Neurosci. 2016 Nov;39(11):750-762. doi: 10.1016/j.tins.2016.09.003. Epub 2016 Oct 21.
5
How can rAAV-α-synuclein and the fibril α-synuclein models advance our understanding of Parkinson's disease?重组腺相关病毒-α-突触核蛋白和丝状α-突触核蛋白模型如何促进我们对帕金森病的理解？
J Neurochem. 2016 Oct;139 Suppl 1(Suppl 1):131-155. doi: 10.1111/jnc.13627. Epub 2016 May 4.
6
Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line.SH-SY5Y人神经母细胞瘤细胞系的分化
J Vis Exp. 2016 Feb 17(108):53193. doi: 10.3791/53193.
7
Elevated α-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson's patient-derived induced pluripotent stem cells.由SNCA基因三倍体导致的α-突触核蛋白升高会损害帕金森病患者来源的诱导多能干细胞中的神经元分化和成熟。
Cell Death Dis. 2015 Nov 26;6(11):e1994. doi: 10.1038/cddis.2015.318.
8
Progressive aggregation of alpha-synuclein and selective degeneration of lewy inclusion-bearing neurons in a mouse model of parkinsonism.帕金森病小鼠模型中α-突触核蛋白的进行性聚集及含路易小体神经元的选择性变性。
Cell Rep. 2015 Mar 3;10(8):1252-60. doi: 10.1016/j.celrep.2015.01.060. Epub 2015 Feb 26.
9
Alpha-synuclein biology in Lewy body diseases.路易体病中的α-突触核蛋白生物学。
Alzheimers Res Ther. 2014 Oct 27;6(5):73. doi: 10.1186/s13195-014-0073-2. eCollection 2014.
10
Intracellular alpha-synuclein affects early maturation of primary oligodendrocyte progenitor cells.细胞内的α-突触核蛋白影响原发性少突胶质前体细胞的早期成熟。
Mol Cell Neurosci. 2014 Sep;62:68-78. doi: 10.1016/j.mcn.2014.06.012. Epub 2014 Jul 11.
Zotero 插件