Rab GTPases 在帕金森病的病理生物学中的作用。
The role of Rab GTPases in the pathobiology of Parkinson' disease.
机构信息
Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Curr Opin Cell Biol. 2019 Aug;59:73-80. doi: 10.1016/j.ceb.2019.03.009. Epub 2019 May 1.
Abstract
Rab GTPases are key regulators of vesicle-mediated transport and are proposed to play a crucial role in the pathobiology of Parkinson's disease. As membrane trafficking seems to be a relevant pathway altered in Parkinson' disease, understanding the role of Rab GTPases in the disease progression could open a window for therapeutic interventions. In this review, we focus on the recent advances on the role of Rab GTPases in the biology of two main proteins involved in Parkinson's disease: LRRK2 and α-synuclein, given that mutations in their genes (LRRK2 and SNCA) cause familial and sporadic Parkinson's disease.
摘要
Rab GTPases 是囊泡介导运输的关键调节剂，据推测在帕金森病的病理生物学中发挥着至关重要的作用。由于膜运输似乎是帕金森病中改变的相关途径，因此了解 Rab GTPases 在疾病进展中的作用可能为治疗干预开辟新的途径。在这篇综述中，我们专注于 Rab GTPases 在两种主要与帕金森病相关的蛋白质（LRRK2 和 α-突触核蛋白）生物学中的最新研究进展，鉴于它们的基因突变（LRRK2 和 SNCA）会导致家族性和散发性帕金森病。
相似文献
1
The role of Rab GTPases in the pathobiology of Parkinson' disease.Rab GTPases 在帕金森病的病理生物学中的作用。
Curr Opin Cell Biol. 2019 Aug;59:73-80. doi: 10.1016/j.ceb.2019.03.009. Epub 2019 May 1.
2
LRRK2 and Rab GTPases.LRRK2 和 Rab GTPases。
Biochem Soc Trans. 2018 Dec 17;46(6):1707-1712. doi: 10.1042/BST20180470. Epub 2018 Nov 22.
3
The emerging role of Rab GTPases in the pathogenesis of Parkinson's disease.Rab GTPases 在帕金森病发病机制中的新兴作用。
Mov Disord. 2018 Feb;33(2):196-207. doi: 10.1002/mds.27270. Epub 2018 Jan 9.
4
Dysregulated phosphorylation of Rab GTPases by LRRK2 induces neurodegeneration.LRRK2 导致 Rab GTPases 的磷酸化失调，从而引发神经退行性变。
Mol Neurodegener. 2018 Feb 13;13(1):8. doi: 10.1186/s13024-018-0240-1.
5
LRRK2 phosphorylation of Rab GTPases in Parkinson's disease.LRRK2 对帕金森病中 Rab GTPases 的磷酸化作用。
FEBS Lett. 2023 Mar;597(6):811-818. doi: 10.1002/1873-3468.14492. Epub 2022 Sep 26.
6
An Update on the Interplay between LRRK2, Rab GTPases and Parkinson's Disease.LRRK2、Rab GTPases 与帕金森病相互作用的最新研究进展。
Biomolecules. 2023 Nov 13;13(11):1645. doi: 10.3390/biom13111645.
7
The Role of LRRK2 in Intracellular Organelle Dynamics.LRRK2 在细胞内细胞器动态中的作用。
J Mol Biol. 2023 Jun 15;435(12):167998. doi: 10.1016/j.jmb.2023.167998. Epub 2023 Feb 9.
8
Rab regulation by GEFs and GAPs during membrane traffic.Rab 的 GEFs 和 GAPs 在膜运输过程中的调节作用。
Curr Opin Cell Biol. 2019 Aug;59:34-39. doi: 10.1016/j.ceb.2019.03.004. Epub 2019 Apr 10.
9
The Cell Biology of LRRK2 in Parkinson's Disease.LRRK2 在帕金森病中的细胞生物学。
Mol Cell Biol. 2021 Apr 22;41(5). doi: 10.1128/MCB.00660-20.
10
Alterations in late endocytic trafficking related to the pathobiology of LRRK2-linked Parkinson's disease.与LRRK2相关帕金森病病理生物学相关的晚期内吞运输改变。
Biochem Soc Trans. 2015 Jun;43(3):390-5. doi: 10.1042/BST20140301.
引用本文的文献
1
Alternative pre-mRNA Splicing and Gene Expression Patterns in Midbrain Lineage Cells Carrying Familial Parkinson's Disease Mutations.携带家族性帕金森病突变的中脑谱系细胞中的可变前体mRNA剪接和基因表达模式
bioRxiv. 2025 Sep 4:2024.02.28.582420. doi: 10.1101/2024.02.28.582420.
2
Engineering a cell-based orthogonal ubiquitin transfer cascade for profiling the substrates of RBR E3 Parkin.构建基于细胞的正交泛素转移级联反应以分析RBR E3泛素连接酶帕金的底物。
iScience. 2025 Jun 17;28(7):112913. doi: 10.1016/j.isci.2025.112913. eCollection 2025 Jul 18.
3
Recent advances in targeting LRRK2 for Parkinson's disease treatment.针对帕金森病治疗靶向亮氨酸丰富重复激酶2（LRRK2）的最新进展。
J Transl Med. 2025 Jul 8;23(1):754. doi: 10.1186/s12967-025-06354-0.
4
Rare Copy Number Variants Intersecting Parkinson's-associated Genes in a Cohort of children With Autism Spectrum Disorders.在一组自闭症谱系障碍儿童中与帕金森相关基因相交的罕见拷贝数变异
Neurosci Insights. 2025 Jun 4;20:26331055251334595. doi: 10.1177/26331055251334595. eCollection 2025.
5
LRRK2-mediated mitochondrial dysfunction in Parkinson's disease.帕金森病中由LRRK2介导的线粒体功能障碍
Biochem J. 2025 May 28;482(11):BCJ20253062. doi: 10.1042/BCJ20253062.
6
Endosomal protein DENND10 promotes developmental competence of neurite extension.内涵体蛋白DENND10促进神经突延伸的发育能力。
iScience. 2025 Apr 8;28(5):112385. doi: 10.1016/j.isci.2025.112385. eCollection 2025 May 16.
7
Rab27b Promotes Lysosomal Function and Alpha-Synuclein Clearance in Neurons.Rab27b促进神经元中的溶酶体功能及α-突触核蛋白清除。
J Neurosci. 2025 Apr 2;45(14):e1579242025. doi: 10.1523/JNEUROSCI.1579-24.2025.
8
Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase-dependent mechanism.通过一种依赖LRRK2激酶的机制对LRRK2 Roc G结构域进行分子内反馈调节。
Elife. 2024 Dec 19;12:RP91083. doi: 10.7554/eLife.91083.
9
Rab Geranylgeranyltransferase Subunit Beta as a Potential Indicator to Assess the Progression of Amyotrophic Lateral Sclerosis.Rab geranylgeranyl转移酶亚基β作为评估肌萎缩侧索硬化症进展的潜在指标。
Brain Sci. 2023 Oct 30;13(11):1531. doi: 10.3390/brainsci13111531.
10
The Role of Rab Proteins in Mitophagy: Insights into Neurodegenerative Diseases.Rab 蛋白在自噬中的作用：对神经退行性疾病的深入了解。
Int J Mol Sci. 2023 Mar 27;24(7):6268. doi: 10.3390/ijms24076268.
本文引用的文献
1
Distinct functional roles of Vps41-mediated neuroprotection in Alzheimer's and Parkinson's disease models of neurodegeneration.Vps41 介导的神经保护在阿尔茨海默病和帕金森病神经退行性模型中的不同功能作用。
Hum Mol Genet. 2018 Dec 15;27(24):4176-4193. doi: 10.1093/hmg/ddy308.
2
RAB7L1-Mediated Relocalization of LRRK2 to the Golgi Complex Causes Centrosomal Deficits via RAB8A.RAB7L1介导的LRRK2重新定位至高尔基体复合体通过RAB8A导致中心体缺陷。
Front Mol Neurosci. 2018 Nov 13;11:417. doi: 10.3389/fnmol.2018.00417. eCollection 2018.
3
The role of monogenic genes in idiopathic Parkinson's disease.单基因在特发性帕金森病中的作用。
Neurobiol Dis. 2019 Apr;124:230-239. doi: 10.1016/j.nbd.2018.11.012. Epub 2018 Nov 15.
4
A pathway for Parkinson's Disease LRRK2 kinase to block primary cilia and Sonic hedgehog signaling in the brain.帕金森病 LRRK2 激酶阻断大脑中的初级纤毛和 Sonic hedgehog 信号通路。
Elife. 2018 Nov 6;7:e40202. doi: 10.7554/eLife.40202.
5
Abrogating Native α-Synuclein Tetramers in Mice Causes a L-DOPA-Responsive Motor Syndrome Closely Resembling Parkinson's Disease.在小鼠中消除内源性α-突触核蛋白四聚体导致一种类似于帕金森病的 L-DOPA 反应性运动综合征。
Neuron. 2018 Oct 10;100(1):75-90.e5. doi: 10.1016/j.neuron.2018.09.014.
6
LRRK2 and its substrate Rab GTPases are sequentially targeted onto stressed lysosomes and maintain their homeostasis.LRRK2 及其底物 Rab GTPases 被顺序靶向到应激溶酶体上，并维持其体内平衡。
Proc Natl Acad Sci U S A. 2018 Sep 25;115(39):E9115-E9124. doi: 10.1073/pnas.1812196115. Epub 2018 Sep 12.
7
LRRK2 kinase regulates α-synuclein propagation via RAB35 phosphorylation.LRRK2 激酶通过 RAB35 磷酸化调节α-突触核蛋白的传播。
Nat Commun. 2018 Aug 27;9(1):3465. doi: 10.1038/s41467-018-05958-z.
8
Mechanisms of lysosomal positioning and movement.溶酶体定位和运动的机制。
Traffic. 2018 Oct;19(10):761-769. doi: 10.1111/tra.12587. Epub 2018 Jul 17.
9
FYCO1 mediates clearance of α-synuclein aggregates through a Rab7-dependent mechanism.FYCO1 通过 Rab7 依赖性机制介导α-突触核蛋白聚集体的清除。
J Neurochem. 2018 Aug;146(4):474-492. doi: 10.1111/jnc.14461. Epub 2018 Jul 23.
10
Genetic risk factors in Parkinson's disease.帕金森病的遗传风险因素。
Cell Tissue Res. 2018 Jul;373(1):9-20. doi: 10.1007/s00441-018-2817-y. Epub 2018 Mar 13.
Zotero 插件