自噬对避免神经退行性变的作用。
Autophagy for the avoidance of neurodegeneration.
作者信息
Madeo Frank, Eisenberg Tobias, Kroemer Guido
机构信息
Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
出版信息
Genes Dev. 2009 Oct 1;23(19):2253-9. doi: 10.1101/gad.1858009.
Abstract
Cellular defense mechanisms, including the unfolded protein response (UPR) and autophagy, attempt to resolve toxic protein aggregates, which are common denominators of neurodegenerative diseases. In this issue of Genes & Development, Hetz and colleagues (pp. 2294-2306) surprisingly show that inhibition of the UPR by knockout of XBP-1 causes a massive increase in autophagy, enhances clearance of superoxide dismutase 1 (SOD1) aggregates, and delays the development of amyotrophic lateral sclerosis. These findings suggest the existence of a homeostatic-if not hormetic-balance between distinct cellular defense mechanisms.
摘要
细胞防御机制，包括未折叠蛋白反应（UPR）和自噬，试图清除有毒蛋白质聚集体，而这些聚集体是神经退行性疾病的共同特征。在本期《基因与发育》中，赫茨及其同事（第2294 - 2306页）令人惊讶地发现，通过敲除XBP - 1来抑制UPR会导致自噬大量增加，增强超氧化物歧化酶1（SOD1）聚集体的清除，并延缓肌萎缩侧索硬化症的发展。这些发现表明，在不同的细胞防御机制之间存在一种稳态——即便不是兴奋性的——平衡。
相似文献
1
Autophagy for the avoidance of neurodegeneration.自噬对避免神经退行性变的作用。
Genes Dev. 2009 Oct 1;23(19):2253-9. doi: 10.1101/gad.1858009.
2
XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy.神经系统中XBP-1的缺失通过增强自噬作用来预防肌萎缩侧索硬化症。
Genes Dev. 2009 Oct 1;23(19):2294-306. doi: 10.1101/gad.1830709. Epub 2009 Sep 17.
3
The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS).小分子热休克蛋白 B8（HspB8）可促进自噬清除与肌萎缩侧索硬化症（ALS）相关的错误折叠蛋白。
Hum Mol Genet. 2010 Sep 1;19(17):3440-56. doi: 10.1093/hmg/ddq257. Epub 2010 Jun 22.
4
XBP-1 deficiency in the nervous system reveals a homeostatic switch to activate autophagy.神经系统中 XBP-1 的缺失揭示了一种激活自噬的体内平衡开关。
Autophagy. 2009 Nov;5(8):1226-8. doi: 10.4161/auto.5.8.10247. Epub 2009 Nov 6.
5
Hypoxia causes autophagic stress and derangement of metabolic adaptation in a cell model of amyotrophic lateral sclerosis.缺氧导致肌萎缩侧索硬化症细胞模型中的自噬应激和代谢适应失调。
J Neurochem. 2014 May;129(3):413-25. doi: 10.1111/jnc.12642. Epub 2014 Jan 22.
6
Stress signaling from the endoplasmic reticulum: A central player in the pathogenesis of amyotrophic lateral sclerosis.内质网应激信号：肌萎缩侧索硬化症发病机制中的核心角色。
IUBMB Life. 2011 Sep;63(9):754-63. doi: 10.1002/iub.520. Epub 2011 Aug 10.
7
Beclin1 decreases the RIPA-insoluble fraction of amyotrophic lateral sclerosis-linked SOD1 mutant via autophagy.Beclin1通过自噬减少肌萎缩侧索硬化症相关SOD1突变体的RIPA不溶性部分。
Neurosci Lett. 2019 Jan 18;690:106-111. doi: 10.1016/j.neulet.2018.10.025. Epub 2018 Oct 12.
8
XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response.XBP-1在未折叠蛋白反应中调节内质网驻留伴侣蛋白基因的一个子集。
Mol Cell Biol. 2003 Nov;23(21):7448-59. doi: 10.1128/MCB.23.21.7448-7459.2003.
9
The debated toxic role of aggregated TDP-43 in amyotrophic lateral sclerosis: a resolution in sight?TDP-43 聚集在肌萎缩侧索硬化症中的争议性毒性作用：是否有解决的希望？
Brain. 2019 May 1;142(5):1176-1194. doi: 10.1093/brain/awz078.
10
Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons.海藻糖通过增强运动神经元中的自噬作用来延缓肌萎缩侧索硬化症的进展。
Autophagy. 2013 Sep;9(9):1308-20. doi: 10.4161/auto.25188. Epub 2013 Jun 6.
引用本文的文献
1
Autophagy Activation Promoted by Pulses of Light and Phytochemicals Counteracting Oxidative Stress during Age-Related Macular Degeneration.光脉冲和植物化学物质促进自噬激活，以对抗年龄相关性黄斑变性期间的氧化应激。
Antioxidants (Basel). 2023 May 30;12(6):1183. doi: 10.3390/antiox12061183.
2
The Essential Role of Light-Induced Autophagy in the Inner Choroid/Outer Retinal Neurovascular Unit in Baseline Conditions and Degeneration.光诱导自噬在正常和变性情况下脉络膜/视网膜外层神经血管单元中的基本作用。
Int J Mol Sci. 2023 May 19;24(10):8979. doi: 10.3390/ijms24108979.
3
Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection.伴侣蛋白依赖的机制作为神经保护的药理学靶点。
Int J Mol Sci. 2023 Jan 3;24(1):823. doi: 10.3390/ijms24010823.
4
A Charcot-Marie-Tooth-Causing Mutation in HSPB1 Decreases Cell Adaptation to Repeated Stress by Disrupting Autophagic Clearance of Misfolded Proteins.HSPB1 中的一种引起夏科-马里-图思病的突变通过破坏错误折叠蛋白的自噬清除来降低细胞对重复应激的适应能力。
Cells. 2022 Sep 15;11(18):2886. doi: 10.3390/cells11182886.
5
ATase inhibition rescues age-associated proteotoxicity of the secretory pathway.ATase 抑制可挽救分泌途径相关的与年龄相关的蛋白毒性。
Commun Biol. 2022 Feb 25;5(1):173. doi: 10.1038/s42003-022-03118-0.
6
Regulation of neuronal autophagy and the implications in neurodegenerative diseases.神经元自噬的调节及其在神经退行性疾病中的意义。
Neurobiol Dis. 2022 Jan;162:105582. doi: 10.1016/j.nbd.2021.105582. Epub 2021 Dec 7.
7
Lactoferrin Protects against Methamphetamine Toxicity by Modulating Autophagy and Mitochondrial Status.乳铁蛋白通过调节自噬和线粒体状态来抵抗甲基苯丙胺毒性。
Nutrients. 2021 Sep 25;13(10):3356. doi: 10.3390/nu13103356.
8
Norepinephrine Protects against Methamphetamine Toxicity through β2-Adrenergic Receptors Promoting LC3 Compartmentalization.去甲肾上腺素通过β2-肾上腺素能受体促进 LC3 隔室化来保护对抗甲基苯丙胺毒性。
Int J Mol Sci. 2021 Jul 5;22(13):7232. doi: 10.3390/ijms22137232.
9
Endoplasmic reticulum acetyltransferases Atase1 and Atase2 differentially regulate reticulophagy, macroautophagy and cellular acetyl-CoA metabolism.内质网乙酰转移酶 Atase1 和 Atase2 差异调节网质体自噬、巨自噬和细胞乙酰辅酶 A 代谢。
Commun Biol. 2021 Apr 12;4(1):454. doi: 10.1038/s42003-021-01992-8.
10
Spreading of pathological TDP-43 along corticospinal tract axons induces ALS-like phenotypes in Atg5 mice.病理 TDP-43 在皮质脊髓束轴突中的扩散导致 Atg5 小鼠出现类似 ALS 的表型。
Int J Biol Sci. 2021 Jan 1;17(2):390-401. doi: 10.7150/ijbs.53872. eCollection 2021.
本文引用的文献
1
XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy.神经系统中XBP-1的缺失通过增强自噬作用来预防肌萎缩侧索硬化症。
Genes Dev. 2009 Oct 1;23(19):2294-306. doi: 10.1101/gad.1830709. Epub 2009 Sep 17.
2
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice.在生命后期喂食雷帕霉素可延长基因异质小鼠的寿命。
Nature. 2009 Jul 16;460(7253):392-5. doi: 10.1038/nature08221. Epub 2009 Jul 8.
3
Autophagy is required for extension of yeast chronological life span by rapamycin.雷帕霉素通过自噬延长酵母的程序性寿命。
Autophagy. 2009 Aug;5(6):847-9. doi: 10.4161/auto.8824. Epub 2009 Aug 23.
4
[Update on fundamental and clinical research in amyotrophic lateral sclerosis].[肌萎缩侧索硬化症的基础与临床研究进展]
Rev Neurol (Paris). 2009 Jun-Jul;165(6-7):532-41. doi: 10.1016/j.neurol.2009.01.038. Epub 2009 May 5.
5
Endoplasmic reticulum protein quality control in neurodegenerative disease: the good, the bad and the therapy.神经退行性疾病中的内质网蛋白质质量控制：益处、危害与治疗
Curr Med Chem. 2009;16(5):615-26. doi: 10.2174/092986709787458506.
6
Protective effect against Parkinson's disease-related insults through the activation of XBP1.通过激活XBP1对帕金森病相关损伤产生保护作用。
Brain Res. 2009 Feb 27;1257:16-24. doi: 10.1016/j.brainres.2008.11.104. Epub 2008 Dec 16.
7
Autophagy is involved in the ischemic preconditioning.自噬参与了缺血预处理。
Neurosci Lett. 2009 Feb 13;451(1):16-9. doi: 10.1016/j.neulet.2008.12.019. Epub 2008 Dec 16.
8
Lithium may be useful in the prevention of Alzheimer's disease in individuals at risk of presenile familial Alzheimer's disease.锂对于预防有早发性家族性阿尔茨海默病风险的个体患阿尔茨海默病可能有用。
Med Hypotheses. 2008 Dec;71(6):948-51. doi: 10.1016/j.mehy.2008.03.049. Epub 2008 Aug 28.
9
The effects of p53 on whole organism longevity are mediated by autophagy.p53 对整个生物体寿命的影响是由自噬介导的。
Autophagy. 2008 Oct;4(7):870-3. doi: 10.4161/auto.6730. Epub 2008 Oct 4.
10
Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function.衰老肝脏中伴侣介导自噬的恢复可改善细胞维持和肝功能。
Nat Med. 2008 Sep;14(9):959-65. doi: 10.1038/nm.1851.
Zotero 插件