TFEB：帕金森病中的致病作用和治疗靶点。
TFEB: Pathogenic role and therapeutic target in Parkinson disease.
机构信息
Department of Experimental Medical Sciences; Wallenberg Neuroscience Center; Lund University; Lund, Skane Sweden.
出版信息
Autophagy. 2013 Aug;9(8):1244-6. doi: 10.4161/auto.25044. Epub 2013 May 22.
Abstract
Parkinson disease (PD) is characterized by the progressive loss of nigral dopamine neurons and the presence of accumulations containing the disease-causing protein SNCA/α-synuclein. Here we review our recent findings describing how SNCA impairs the function of the master regulator of the autophagy-lysosomal pathway (ALP), the transcription factor EB (TFEB), and that genetic or pharmacological stimulation of its activity promotes protection of dopamine neurons. These findings suggest that strategies aimed at enhancing autophagy-mediated degradation of SNCA may hold great promise for disease intervention in PD.
摘要
帕金森病（PD）的特征是黑质多巴胺神经元的进行性丧失和含有致病蛋白 SNCA/α-突触核蛋白的堆积物的存在。在这里，我们回顾了我们最近的发现，描述了 SNCA 如何损害自噬溶酶体途径 (ALP) 的主调控因子转录因子 EB (TFEB) 的功能，以及其活性的遗传或药理学刺激如何促进多巴胺神经元的保护。这些发现表明，旨在增强 SNCA 介导的自噬降解的策略可能为 PD 疾病干预提供巨大的希望。
相似文献
1
TFEB: Pathogenic role and therapeutic target in Parkinson disease.TFEB：帕金森病中的致病作用和治疗靶点。
Autophagy. 2013 Aug;9(8):1244-6. doi: 10.4161/auto.25044. Epub 2013 May 22.
2
TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity.TFEB 介导的自噬可挽救中脑多巴胺神经元免受α-突触核蛋白毒性的影响。
Proc Natl Acad Sci U S A. 2013 May 7;110(19):E1817-26. doi: 10.1073/pnas.1305623110. Epub 2013 Apr 22.
3
Restoring impaired protein metabolism in Parkinson's disease--TFEB-mediated autophagy as a novel therapeutic target.恢复帕金森病中受损的蛋白质代谢——TFEB介导的自噬作为一种新的治疗靶点。
Mov Disord. 2013 Sep;28(10):1346. doi: 10.1002/mds.25601.
4
Transcription factor EB overexpression prevents neurodegeneration in experimental synucleinopathies.转录因子 EB 过表达可预防实验性突触核蛋白病中的神经退行性变。
JCI Insight. 2019 Aug 22;4(16):129719. doi: 10.1172/jci.insight.129719.
5
Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA).帕金森病突变 LRRK2 敲入小鼠模型中，由于降解受损导致寡聚化 SNCA/α-突触核蛋白的年龄依赖性积累：伴侣介导的自噬 (CMA) 治疗激活的作用。
Autophagy. 2020 Feb;16(2):347-370. doi: 10.1080/15548627.2019.1603545. Epub 2019 Apr 14.
6
The Autophagy-Lysosomal Pathway in Neurodegeneration: A TFEB Perspective.神经退行性变中的自噬-溶酶体途径：从转录因子EB（TFEB）角度的探讨
Trends Neurosci. 2016 Apr;39(4):221-234. doi: 10.1016/j.tins.2016.02.002. Epub 2016 Mar 9.
7
Neuronal-targeted TFEB rescues dysfunction of the autophagy-lysosomal pathway and alleviates ischemic injury in permanent cerebral ischemia.神经元靶向 TFEB 挽救自噬溶酶体途径的功能障碍并减轻永久性脑缺血中的缺血性损伤。
Autophagy. 2019 Mar;15(3):493-509. doi: 10.1080/15548627.2018.1531196. Epub 2018 Oct 18.
8
Genetic and chemical activation of TFEB mediates clearance of aggregated α-synuclein.TFEB的基因和化学激活介导聚集的α-突触核蛋白的清除。
PLoS One. 2015 Mar 19;10(3):e0120819. doi: 10.1371/journal.pone.0120819. eCollection 2015.
9
A Curcumin Derivative Activates TFEB and Protects Against Parkinsonian Neurotoxicity .姜黄素衍生物激活 TFEB 并防止帕金森病神经毒性。
Int J Mol Sci. 2020 Feb 22;21(4):1515. doi: 10.3390/ijms21041515.
10
Activation of ROS-PERK-TFEB by filbertone ameliorates neurodegenerative diseases via enhancing the autophagy-lysosomal pathway.榛子酮通过激活 ROS-PERK-TFEB 来改善神经退行性疾病，增强自噬溶酶体通路。
J Nutr Biochem. 2023 Aug;118:109325. doi: 10.1016/j.jnutbio.2023.109325. Epub 2023 Mar 22.
引用本文的文献
1
Small-molecule activation of TFEB alleviates Niemann-Pick disease type C via promoting lysosomal exocytosis and biogenesis.通过促进溶酶体胞吐作用和生物发生，小分子激活转录因子EB可缓解C型尼曼-匹克病。
Elife. 2025 Apr 4;13:RP103137. doi: 10.7554/eLife.103137.
2
ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease.ZKSCAN3通过转录因子EB影响帕金森病中的自噬-溶酶体途径。
Biomed Rep. 2025 Feb 25;22(4):74. doi: 10.3892/br.2025.1952. eCollection 2025 Apr.
3
The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy through TFEB.雌激素受体相关孤儿受体通过 TFEB 调节自噬。
Mol Pharmacol. 2024 Sep 17;106(4):164-172. doi: 10.1124/molpharm.124.000889.
4
Deregulation of mTORC1-TFEB axis in human iPSC model of -associated Parkinson's disease.与相关帕金森病的人类诱导多能干细胞模型中mTORC1-TFEB轴的失调。
Front Neurosci. 2023 Jun 2;17:1152503. doi: 10.3389/fnins.2023.1152503. eCollection 2023.
5
Histone Deacetylase 4 Inhibition Reduces Rotenone-Induced Alpha-Synuclein Accumulation via Autophagy in SH-SY5Y Cells.组蛋白去乙酰化酶4抑制通过自噬减少鱼藤酮诱导的SH-SY5Y细胞中α-突触核蛋白的积累。
Brain Sci. 2023 Apr 16;13(4):670. doi: 10.3390/brainsci13040670.
6
Alpha-Synuclein: The Spark That Flames Dopaminergic Neurons, In Vitro and In Vivo Evidence.α-突触核蛋白：点燃多巴胺能神经元的火花，体外和体内证据。
Int J Mol Sci. 2022 Aug 30;23(17):9864. doi: 10.3390/ijms23179864.
7
The Common Cellular Events in the Neurodegenerative Diseases and the Associated Role of Endoplasmic Reticulum Stress.神经退行性疾病中的常见细胞事件及内质网应激的相关作用。
Int J Mol Sci. 2022 May 24;23(11):5894. doi: 10.3390/ijms23115894.
8
Over-Mutated Mitochondrial, Lysosomal and TFEB-Regulated Genes in Parkinson's Disease.帕金森病中过度突变的线粒体、溶酶体及受转录因子EB调控的基因
J Clin Med. 2022 Mar 21;11(6):1749. doi: 10.3390/jcm11061749.
9
Transcriptional analysis of peripheral memory T cells reveals Parkinson's disease-specific gene signatures.外周记忆T细胞的转录分析揭示帕金森病特异性基因特征。
NPJ Parkinsons Dis. 2022 Mar 21;8(1):30. doi: 10.1038/s41531-022-00282-2.
10
Ellagic Acid Prevents α-Synuclein Aggregation and Protects SH-SY5Y Cells from Aggregated α-Synuclein-Induced Toxicity via Suppression of Apoptosis and Activation of Autophagy.鞣花酸通过抑制细胞凋亡和激活自噬来防止α-突触核蛋白聚集，并保护 SH-SY5Y 细胞免受聚集的α-突触核蛋白诱导的毒性。
Int J Mol Sci. 2021 Dec 13;22(24):13398. doi: 10.3390/ijms222413398.
Zotero 插件