亨廷顿舞蹈症中线粒体运输受损。
Impaired mitochondrial trafficking in Huntington's disease.
作者信息
Li Xiao-Jiang, Orr Adam L, Li Shihua
机构信息
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
出版信息
Biochim Biophys Acta. 2010 Jan;1802(1):62-5. doi: 10.1016/j.bbadis.2009.06.008. Epub 2009 Jul 8.
Abstract
Impaired mitochondrial function has been well documented in Huntington's disease. Mutant huntingtin is found to affect mitochondria via various mechanisms including the dysregulation of gene transcription and impairment of mitochondrial function or trafficking. The lengthy and highly branched neuronal processes constitute complex neural networks in which there is a large demand for mitochondria-generated energy. Thus, the impaired mitochondrial trafficking in neuronal cells may play an important role in the selective neuropathology of Huntington's disease. Here we discuss the evidence for the effect of the Huntington's disease protein huntingtin on the intracellular trafficking of mitochondria and the involvement of this defective trafficking in the pathogenesis of Huntington's disease.
摘要
线粒体功能受损在亨廷顿舞蹈病中已有充分记载。已发现突变的亨廷顿蛋白通过多种机制影响线粒体，包括基因转录失调以及线粒体功能或运输受损。冗长且高度分支的神经元突起构成了复杂的神经网络，其中对线粒体产生的能量有大量需求。因此，神经元细胞中线粒体运输受损可能在亨廷顿舞蹈病的选择性神经病理学中起重要作用。在此，我们讨论亨廷顿舞蹈病蛋白亨廷顿对线粒体细胞内运输影响的证据，以及这种有缺陷的运输在亨廷顿舞蹈病发病机制中的作用。
相似文献
1
Impaired mitochondrial trafficking in Huntington's disease.亨廷顿舞蹈症中线粒体运输受损。
Biochim Biophys Acta. 2010 Jan;1802(1):62-5. doi: 10.1016/j.bbadis.2009.06.008. Epub 2009 Jul 8.
2
Huntington's Disease and Mitochondria.亨廷顿病与线粒体。
Neurotox Res. 2017 Oct;32(3):518-529. doi: 10.1007/s12640-017-9766-1. Epub 2017 Jun 21.
3
Mitochondrial dynamics and quality control in Huntington's disease.亨廷顿病中的线粒体动态和质量控制。
Neurobiol Dis. 2016 Jun;90:51-7. doi: 10.1016/j.nbd.2015.09.008. Epub 2015 Sep 24.
4
Olesoxime suppresses calpain activation and mutant huntingtin fragmentation in the BACHD rat.奥昔莫司汀抑制 BACHD 大鼠钙蛋白酶激活和突变 huntingtin 片段化。
Brain. 2015 Dec;138(Pt 12):3632-53. doi: 10.1093/brain/awv290. Epub 2015 Oct 21.
5
Mutant huntingtin, abnormal mitochondrial dynamics, defective axonal transport of mitochondria, and selective synaptic degeneration in Huntington's disease.突变型亨廷顿蛋白、异常的线粒体动力学、线粒体轴突运输缺陷以及亨廷顿病中的选择性突触退化。
Biochim Biophys Acta. 2012 Feb;1822(2):101-10. doi: 10.1016/j.bbadis.2011.10.016. Epub 2011 Nov 4.
6
The role of mitochondrial dysfunction in Huntington's disease: Implications for therapeutic targeting.线粒体功能障碍在亨廷顿舞蹈病中的作用：对治疗靶点的启示。
Biomed Pharmacother. 2025 Feb;183:117827. doi: 10.1016/j.biopha.2025.117827. Epub 2025 Jan 23.
7
Mitochondrial dysfunction, metabolic deficits, and increased oxidative stress in Huntington's disease.亨廷顿舞蹈症中的线粒体功能障碍、代谢缺陷及氧化应激增加
Chang Gung Med J. 2011 Mar-Apr;34(2):135-52.
8
S-nitrosylation of dynamin-related protein 1 mediates mutant huntingtin-induced mitochondrial fragmentation and neuronal injury in Huntington's disease.DRP1 的 S-亚硝基化介导突变 huntingtin 诱导的亨廷顿病中线粒体片段化和神经元损伤。
Antioxid Redox Signal. 2013 Oct 10;19(11):1173-84. doi: 10.1089/ars.2012.4928. Epub 2013 Jun 20.
9
Drp1/Fis1-mediated mitochondrial fragmentation leads to lysosomal dysfunction in cardiac models of Huntington's disease.Drp1/Fis1 介导的线粒体片段化导致亨廷顿病心脏模型中的溶酶体功能障碍。
J Mol Cell Cardiol. 2019 Feb;127:125-133. doi: 10.1016/j.yjmcc.2018.12.004. Epub 2018 Dec 11.
10
Downregulation of glial genes involved in synaptic function mitigates Huntington's disease pathogenesis.下调与突触功能相关的神经胶质基因可减轻亨廷顿病的发病机制。
Elife. 2021 Apr 19;10:e64564. doi: 10.7554/eLife.64564.
引用本文的文献
1
Sculpting excitable membranes: voltage-gated ion channel delivery and distribution.塑造可兴奋膜：电压门控离子通道的转运与分布。
Nat Rev Neurosci. 2025 Apr 2. doi: 10.1038/s41583-025-00917-2.
2
Iron homeostasis imbalance and ferroptosis in brain diseases.脑疾病中的铁稳态失衡与铁死亡
MedComm (2020). 2023 Jun 26;4(4):e298. doi: 10.1002/mco2.298. eCollection 2023 Aug.
3
An analysis of neurovascular disease markers in the hippocampus of at different growth stages.不同生长阶段海马体中神经血管疾病标志物的分析。
Front Neurol. 2023 Jan 17;13:1083182. doi: 10.3389/fneur.2022.1083182. eCollection 2022.
4
In Vivo Imaging of Axonal Organelle Transport in the Mouse Brain.小鼠脑内轴突细胞器运输的活体成像
Methods Mol Biol. 2022;2431:95-109. doi: 10.1007/978-1-0716-1990-2_5.
5
Structural Plasticity of the Hippocampus in Neurodegenerative Diseases.神经退行性疾病中海马的结构可塑性。
Int J Mol Sci. 2022 Mar 20;23(6):3349. doi: 10.3390/ijms23063349.
6
Small Molecule Improvement of Trafficking Defects in Models of Neurodegeneration.小分子改善神经退行性模型中的运输缺陷。
ACS Chem Neurosci. 2021 Nov 3;12(21):3972-3984. doi: 10.1021/acschemneuro.1c00524. Epub 2021 Oct 15.
7
D1R- and D2R-Medium-Sized Spiny Neurons Diversity: Insights Into Striatal Vulnerability to Huntington's Disease Mutation.D1R和D2R中型多棘神经元的多样性：对纹状体易受亨廷顿舞蹈症突变影响的见解
Front Cell Neurosci. 2021 Feb 10;15:628010. doi: 10.3389/fncel.2021.628010. eCollection 2021.
8
Developmental Trajectory of Height, Weight, and BMI in Children and Adolescents at Risk for Huntington's Disease: Effect of mHTT on Growth.亨廷顿病高危儿童和青少年的身高、体重和 BMI 的发育轨迹：mHTT 对生长的影响。
J Huntingtons Dis. 2020;9(3):245-251. doi: 10.3233/JHD-200407.
9
Impaired response of cerebral oxygen metabolism to visual stimulation in Huntington's disease.亨廷顿舞蹈症患者大脑氧代谢对视觉刺激的反应受损。
J Cereb Blood Flow Metab. 2021 May;41(5):1119-1130. doi: 10.1177/0271678X20949286. Epub 2020 Aug 17.
10
Expression of Human Mutant Huntingtin Protein in Hemocytes Impairs Immune Responses.人突变亨廷顿蛋白在血淋巴细胞中的表达损害免疫反应。
Front Immunol. 2019 Oct 16;10:2405. doi: 10.3389/fimmu.2019.02405. eCollection 2019.
本文引用的文献
1
Differential activities of the ubiquitin-proteasome system in neurons versus glia may account for the preferential accumulation of misfolded proteins in neurons.神经元与神经胶质细胞中泛素-蛋白酶体系统的不同活性可能是错误折叠蛋白在神经元中优先积累的原因。
J Neurosci. 2008 Dec 3;28(49):13285-95. doi: 10.1523/JNEUROSCI.4393-08.2008.
2
Mutant huntingtin and mitochondrial dysfunction.突变型亨廷顿蛋白与线粒体功能障碍
Trends Neurosci. 2008 Dec;31(12):609-16. doi: 10.1016/j.tins.2008.09.004. Epub 2008 Oct 24.
3
Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons.亨廷顿蛋白磷酸化作为神经元中顺行/逆行运输的分子开关。
EMBO J. 2008 Aug 6;27(15):2124-34. doi: 10.1038/emboj.2008.133. Epub 2008 Jul 10.
4
Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin.细胞内抗体对神经毡聚集体和神经症状的抑制表明突变亨廷顿蛋白具有细胞质毒性。
J Cell Biol. 2008 Jun 2;181(5):803-16. doi: 10.1083/jcb.200710158. Epub 2008 May 26.
5
Impaired ubiquitin-proteasome system activity in the synapses of Huntington's disease mice.亨廷顿舞蹈症小鼠突触中泛素-蛋白酶体系统活性受损。
J Cell Biol. 2008 Mar 24;180(6):1177-89. doi: 10.1083/jcb.200709080.
6
N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking.N端突变型亨廷顿蛋白与线粒体相关联并损害线粒体运输。
J Neurosci. 2008 Mar 12;28(11):2783-92. doi: 10.1523/JNEUROSCI.0106-08.2008.
7
Huntingtin facilitates dynein/dynactin-mediated vesicle transport.亨廷顿蛋白促进动力蛋白/动力蛋白激活蛋白介导的囊泡运输。
Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10045-50. doi: 10.1073/pnas.0610628104. Epub 2007 Jun 4.
8
Oxidative stress and mitochondrial dysfunction in neurodegenerative diseases.神经退行性疾病中的氧化应激与线粒体功能障碍
Neuroscience. 2007 Apr 14;145(4):1233-48. doi: 10.1016/j.neuroscience.2006.10.056. Epub 2007 Feb 14.
9
Multiple pathways contribute to the pathogenesis of Huntington disease.多种途径参与亨廷顿舞蹈症的发病机制。
Mol Neurodegener. 2006 Dec 16;1:19. doi: 10.1186/1750-1326-1-19.
10
The first 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis.亨廷顿蛋白的前17个氨基酸调节其亚细胞定位、聚集以及对钙稳态的影响。
Hum Mol Genet. 2007 Jan 1;16(1):61-77. doi: 10.1093/hmg/ddl440. Epub 2006 Nov 29.
Zotero 插件