内源性α-突触核蛋白影响小鼠黑质多巴胺能神经元的数量。
Endogenous alpha-synuclein influences the number of dopaminergic neurons in mouse substantia nigra.
机构信息
Centre for Brain Repair, Dept. of Clinical Neurosciences, Cambridge, UK.
出版信息
Exp Neurol. 2013 Oct;248:541-5. doi: 10.1016/j.expneurol.2013.07.015. Epub 2013 Aug 8.
Abstract
The presynaptic protein α-synuclein is central to the pathogenesis of α-synucleinopathies. We show that the presence of endogenous mouse α-synuclein leads to higher number of dopaminergic neurons in the substantia nigra of wild-type C57Bl/6J mice compared with C57Bl/6S mice with a spontaneous deletion of the α-synuclein gene or C57Bl/6J mice with a targeted deletion of the α-synuclein gene. This effect of α-synuclein on dopaminergic neuron occurs during development between E10.5 and E13.5 and persists in adult life supporting the involvement of α-synuclein in the development of a subset of dopaminergic neurons.
摘要
突触前蛋白α-突触核蛋白是α-突触核蛋白病发病机制的核心。我们发现，与具有α-突触核蛋白基因自发缺失的 C57Bl/6S 小鼠或α-突触核蛋白基因靶向缺失的 C57Bl/6J 小鼠相比，内源性小鼠α-突触核蛋白的存在导致野生型 C57Bl/6J 小鼠黑质中的多巴胺能神经元数量增加。这种α-突触核蛋白对多巴胺能神经元的影响发生在 E10.5 和 E13.5 之间的发育过程中，并在成年期持续存在，支持α-突触核蛋白参与一部分多巴胺能神经元的发育。
相似文献
1
Endogenous alpha-synuclein influences the number of dopaminergic neurons in mouse substantia nigra.内源性α-突触核蛋白影响小鼠黑质多巴胺能神经元的数量。
Exp Neurol. 2013 Oct;248:541-5. doi: 10.1016/j.expneurol.2013.07.015. Epub 2013 Aug 8.
2
Reduced complement of dopaminergic neurons in the substantia nigra pars compacta of mice with a constitutive "low footprint" genetic knockout of alpha-synuclein.α-突触核蛋白组成型“低足迹”基因敲除小鼠黑质致密部多巴胺能神经元减少。
Mol Brain. 2020 May 11;13(1):75. doi: 10.1186/s13041-020-00613-5.
3
Dopaminergic neuron loss and up-regulation of chaperone protein mRNA induced by targeted over-expression of alpha-synuclein in mouse substantia nigra.小鼠黑质中α-突触核蛋白靶向过表达诱导多巴胺能神经元丢失及伴侣蛋白mRNA上调。
J Neurochem. 2007 Mar;100(6):1449-57. doi: 10.1111/j.1471-4159.2006.04310.x. Epub 2007 Jan 4.
4
Nigral overexpression of alpha-synuclein in the absence of parkin enhances alpha-synuclein phosphorylation but does not modulate dopaminergic neurodegeneration.在缺乏帕金蛋白的情况下，黑质中α-突触核蛋白的过表达会增强α-突触核蛋白的磷酸化，但不会调节多巴胺能神经变性。
Mol Neurodegener. 2015 Jun 23;10:23. doi: 10.1186/s13024-015-0017-8.
5
Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model.α-突触核蛋白致密聚集体的耗散与一种新的帕金森病模型中多巴胺能神经元功能障碍和死亡的挽救有关。
Acta Neuropathol. 2019 Oct;138(4):575-595. doi: 10.1007/s00401-019-02023-x. Epub 2019 May 31.
6
rAAV2/7 vector-mediated overexpression of alpha-synuclein in mouse substantia nigra induces protein aggregation and progressive dose-dependent neurodegeneration.rAAV2/7 载体介导的小鼠黑质中 alpha-突触核蛋白的过表达诱导蛋白聚集和进行性剂量依赖性神经退行性变。
Mol Neurodegener. 2013 Nov 25;8:44. doi: 10.1186/1750-1326-8-44.
7
Viral overexpression of human alpha-synuclein in mouse substantia nigra dopamine neurons results in hyperdopaminergia but no neurodegeneration.人源α-突触核蛋白在小鼠黑质多巴胺神经元中的病毒过表达导致多巴胺能亢进，但无神经退行性变。
Exp Neurol. 2024 Dec;382:114959. doi: 10.1016/j.expneurol.2024.114959. Epub 2024 Sep 15.
8
A dual role for α-synuclein in facilitation and depression of dopamine release from substantia nigra neurons in vivo.α-突触核蛋白在体内促进和抑制黑质神经元多巴胺释放中的双重作用。
Proc Natl Acad Sci U S A. 2020 Dec 22;117(51):32701-32710. doi: 10.1073/pnas.2013652117. Epub 2020 Dec 3.
9
Dopamine and α-synuclein dysfunction in Smad3 null mice.Smad3 基因敲除小鼠模型中的多巴胺和α-突触核蛋白功能障碍。
Mol Neurodegener. 2011 Oct 13;6:72. doi: 10.1186/1750-1326-6-72.
10
Decreased expression of serum- and glucocorticoid-inducible kinase 1 (SGK1) promotes alpha-synuclein increase related with down-regulation of dopaminergic cell in the Substantia Nigra of chronic MPTP-induced Parkinsonism mice and in SH-SY5Y cells.血清和糖皮质激素诱导激酶 1（SGK1）表达降低促进慢性 MPTP 诱导的帕金森病小鼠黑质多巴胺能神经元中与α-突触核蛋白增加相关的下调和 SH-SY5Y 细胞。
Gene. 2018 Jun 30;661:189-195. doi: 10.1016/j.gene.2018.03.086. Epub 2018 Mar 29.
引用本文的文献
1
Contrasting Behavioural and Biochemical Characteristics of Normal and Spontaneously α-Synuclein-Deficient Mice Treated With MPTP.用MPTP处理的正常和自发α-突触核蛋白缺陷小鼠的行为和生化特征对比
J Neurochem. 2025 Aug;169(8):e70201. doi: 10.1111/jnc.70201.
2
Exploring α-Syn's Functions Through Ablation Models: Physiological and Pathological Implications.通过基因敲除模型探索α-突触核蛋白的功能：生理和病理意义
Cell Mol Neurobiol. 2025 May 19;45(1):44. doi: 10.1007/s10571-025-01560-2.
3
Alpha-Synuclein Gene Alterations Modulate Tyrosine Hydroxylase in Human iPSC-Derived Neurons in a Parkinson's Disease Animal Model.α-突触核蛋白基因改变在帕金森病动物模型中调节人诱导多能干细胞衍生神经元中的酪氨酸羟化酶。
Life (Basel). 2024 Jun 5;14(6):728. doi: 10.3390/life14060728.
4
Exploring potential developmental origins of common neurodegenerative disorders.探索常见神经退行性疾病的潜在发育起源。
Biochem Soc Trans. 2024 Jun 26;52(3):1035-1044. doi: 10.1042/BST20230422.
5
The Effects of Serping1 siRNA in α-Synuclein Regulation in MPTP-Induced Parkinson's Disease.Serping1小干扰RNA对MPTP诱导的帕金森病中α-突触核蛋白调控的影响
Biomedicines. 2023 Jul 10;11(7):1952. doi: 10.3390/biomedicines11071952.
6
Unlocking Neural Function with 3D In Vitro Models: A Technical Review of Self-Assembled, Guided, and Bioprinted Brain Organoids and Their Applications in the Study of Neurodevelopmental and Neurodegenerative Disorders.利用 3D 体外模型解锁神经功能：自组装、导向和生物打印脑类器官及其在神经发育和神经退行性疾病研究中的应用的技术综述。
Int J Mol Sci. 2023 Jun 28;24(13):10762. doi: 10.3390/ijms241310762.
7
Studies on alpha-synuclein and islet amyloid polypeptide interaction.α-突触核蛋白与胰岛淀粉样多肽相互作用的研究。
Front Mol Biosci. 2023 Jan 30;10:1080112. doi: 10.3389/fmolb.2023.1080112. eCollection 2023.
8
Alpha-synuclein oligomers alter the spontaneous firing discharge of cultured midbrain neurons.α-突触核蛋白寡聚体改变培养的中脑神经元的自发放电。
Front Cell Neurosci. 2023 Jan 20;17:1078550. doi: 10.3389/fncel.2023.1078550. eCollection 2023.
9
α-Synuclein in synaptic function and dysfunction.α-突触核蛋白在突触功能及功能障碍中的作用。
Trends Neurosci. 2023 Feb;46(2):153-166. doi: 10.1016/j.tins.2022.11.007. Epub 2022 Dec 23.
10
Hunting for Genes Underlying Emotionality in the Laboratory Rat: Maps, Tools and Traps.实验室大鼠情感相关基因的研究：图谱、工具与陷阱。
Curr Neuropharmacol. 2023;21(9):1840-1863. doi: 10.2174/1570159X20666220901154034.
本文引用的文献
1
Role of α-synuclein in adult neurogenesis and neuronal maturation in the dentate gyrus.α-突触核蛋白在齿状回成人神经发生和神经元成熟中的作用。
J Neurosci. 2012 Nov 21;32(47):16906-16. doi: 10.1523/JNEUROSCI.2723-12.2012.
2
α-Synuclein inhibits intersynaptic vesicle mobility and maintains recycling-pool homeostasis.α-突触核蛋白抑制突触间囊泡的流动性并维持循环池的稳态。
J Neurosci. 2012 Jul 25;32(30):10129-35. doi: 10.1523/JNEUROSCI.0535-12.2012.
3
Functional alterations to the nigrostriatal system in mice lacking all three members of the synuclein family.缺失所有三种突触核蛋白家族成员的小鼠黑质纹状体系统的功能改变。
J Neurosci. 2011 May 18;31(20):7264-74. doi: 10.1523/JNEUROSCI.6194-10.2011.
4
Resistance to MPTP-neurotoxicity in α-synuclein knockout mice is complemented by human α-synuclein and associated with increased β-synuclein and Akt activation.α-突触核蛋白敲除小鼠对 MPTP 神经毒性的抗性可被人源 α-突触核蛋白所补充，并与β-突触核蛋白和 Akt 激活增加相关。
PLoS One. 2011 Jan 31;6(1):e16706. doi: 10.1371/journal.pone.0016706.
5
αβγ-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction.αβγ-突触核蛋白三敲除小鼠揭示了年龄依赖性神经元功能障碍。
Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19573-8. doi: 10.1073/pnas.1005005107. Epub 2010 Oct 25.
6
Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro.α-突触核蛋白在体内和体外促进 SNARE 复合物的组装。
Science. 2010 Sep 24;329(5999):1663-7. doi: 10.1126/science.1195227. Epub 2010 Aug 26.
7
Identifying PD-causing genes and genetic susceptibility factors: current approaches and future prospects.鉴定 PD 致病基因和遗传易感因素：当前方法和未来展望。
Prog Brain Res. 2010;183:3-20. doi: 10.1016/S0079-6123(10)83001-8.
8
SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease.帕金森病转基因小鼠模型中的 SNARE 蛋白重分布和突触故障。
Brain. 2010 Jul;133(Pt 7):2032-44. doi: 10.1093/brain/awq132. Epub 2010 Jun 9.
9
Alpha-synuclein sequesters arachidonic acid to modulate SNARE-mediated exocytosis.α-突触核蛋白将花生四烯酸隔离以调节 SNARE 介导的胞吐作用。
EMBO Rep. 2010 Jul;11(7):528-33. doi: 10.1038/embor.2010.66. Epub 2010 May 21.
10
Nurr1 is required for maintenance of maturing and adult midbrain dopamine neurons.Nurr1 对于成熟和成年中脑多巴胺神经元的维持是必需的。
J Neurosci. 2009 Dec 16;29(50):15923-32. doi: 10.1523/JNEUROSCI.3910-09.2009.
Zotero 插件