靶向神经退行性疾病中的自噬：从分子机制到临床治疗。
Targeting autophagy in neurodegenerative diseases: From molecular mechanisms to clinical therapeutics.
机构信息
Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
出版信息
Clin Exp Pharmacol Physiol. 2021 Jul;48(7):943-953. doi: 10.1111/1440-1681.13500. Epub 2021 Apr 21.
Abstract
Many neurodegenerative diseases are associated with pathological aggregation of proteins in neurons. Autophagy is a natural self-cannibalization process that can act as a powerful mechanism to remove aged and damaged organelles as well as protein aggregates. It has been shown that promoting autophagy can attenuate or delay neurodegeneration by removing protein aggregates. In this paper, we will review the role of autophagy in Alzheimer's disease (AD), Parkinson's Disease (PD), and Huntington's Disease (HD) and discuss opportunities and challenges of targeting autophagy as a potential therapeutic avenue for treatment of these common neurodegenerative diseases.
摘要
许多神经退行性疾病都与神经元中蛋白质的病理性聚集有关。自噬是一种自然的自我吞噬过程，可以作为一种强大的机制来清除衰老和受损的细胞器以及蛋白质聚集体。已经表明，通过去除蛋白质聚集体，促进自噬可以减轻或延迟神经退行性变。本文将综述自噬在阿尔茨海默病（AD）、帕金森病（PD）和亨廷顿病（HD）中的作用，并讨论将自噬作为这些常见神经退行性疾病治疗的潜在治疗靶点的机会和挑战。
相似文献
1
Targeting autophagy in neurodegenerative diseases: From molecular mechanisms to clinical therapeutics.
Clin Exp Pharmacol Physiol. 2021 Jul;48(7):943-953. doi: 10.1111/1440-1681.13500. Epub 2021 Apr 21.
2
Targeting autophagy in the brain: a promising approach?
Cent Nerv Syst Agents Med Chem. 2010 Jun 1;10(2):158-68. doi: 10.2174/187152410791196350.
3
Autophagy, its mechanisms and regulation: Implications in neurodegenerative diseases.
Ageing Res Rev. 2017 Nov;40:64-74. doi: 10.1016/j.arr.2017.09.005. Epub 2017 Sep 18.
4
The autophagy-lysosomal degradation pathway: role in neurodegenerative disease and therapy.
Front Biosci. 2008 Jan 1;13:718-36. doi: 10.2741/2714.
5
Mitophagy in neurodegenerative diseases.
Neurochem Int. 2018 Jul;117:156-166. doi: 10.1016/j.neuint.2017.08.004. Epub 2017 Aug 8.
6
Neuronal autophagy and neurodegenerative diseases.
Exp Mol Med. 2012 Feb 29;44(2):89-98. doi: 10.3858/emm.2012.44.2.031.
7
Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies.
Exp Mol Med. 2015 Mar 13;47(3):e147. doi: 10.1038/emm.2014.117.
8
A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Bioactive Peptides.
Curr Protein Pept Sci. 2024;25(7):507-526. doi: 10.2174/0113892037275221240327042353.
9
Regulation of Autophagy in Neurodegenerative Diseases by Natural Products.
Adv Exp Med Biol. 2020;1207:725-730. doi: 10.1007/978-981-15-4272-5_54.
10
Therapeutic induction of autophagy to modulate neurodegenerative disease progression.
Acta Pharmacol Sin. 2013 May;34(5):600-4. doi: 10.1038/aps.2012.189. Epub 2013 Feb 4.
引用本文的文献
1
Research progress on rehabilitation programs for dysphagia in patients with ischemic stroke: A Narrative review.
Pak J Med Sci. 2025 Jul;41(7):2144-2151. doi: 10.12669/pjms.41.7.9657.
2
Autophagy and Cellular Senescence in Alzheimer's Disease: Key Drivers of Neurodegeneration.
CNS Neurosci Ther. 2025 Jul;31(7):e70503. doi: 10.1111/cns.70503.
3
Role of autophagy in neurotoxic protein's clearance following post-ischemic stroke: where we are and what we know?
Mol Brain. 2025 Jul 8;18(1):60. doi: 10.1186/s13041-025-01201-1.
4
Gentiacaulein inhibits glucose transport to induce PRKAA1-mediated autophagy to clear amyloid beta and associated inflammation in primary astrocytes.
Autophagy Rep. 2024 Jan 5;3(1):2296209. doi: 10.1080/27694127.2023.2296209. eCollection 2024.
5
Therapeutic approaches targeting aging and cellular senescence in Huntington's disease.
CNS Neurosci Ther. 2024 Oct;30(10):e70053. doi: 10.1111/cns.70053.
6
From Agriculture to Clinics: Unlocking the Potential of Magnetized Water for Planetary and Human Health.
Cureus. 2024 Jul 8;16(7):e64104. doi: 10.7759/cureus.64104. eCollection 2024 Jul.
7
Cellular and Molecular Responses to Mitochondrial DNA Deletions in Kearns-Sayre Syndrome: Some Underlying Mechanisms.
Mol Neurobiol. 2024 Aug;61(8):5665-5679. doi: 10.1007/s12035-024-03938-7.
8
Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease.
Front Aging Neurosci. 2023 Nov 2;15:1281338. doi: 10.3389/fnagi.2023.1281338. eCollection 2023.
9
Targeting Mitochondrial Dysfunction and Oxidative Stress to Prevent the Neurodegeneration of Retinal Ganglion Cells.
Antioxidants (Basel). 2023 Nov 17;12(11):2011. doi: 10.3390/antiox12112011.
10
A novel link between silent information regulator 1 and autophagy in cerebral ischemia-reperfusion.
Front Neurosci. 2022 Nov 23;16:1040182. doi: 10.3389/fnins.2022.1040182. eCollection 2022.
本文引用的文献
1
ER Stress in Cardiometabolic Diseases: From Molecular Mechanisms to Therapeutics.
Endocr Rev. 2021 Nov 16;42(6):839-871. doi: 10.1210/endrev/bnab006.
2
Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases.
Nat Rev Cardiol. 2021 Jul;18(7):499-521. doi: 10.1038/s41569-021-00511-w. Epub 2021 Feb 22.
3
Prebiotic Lactulose Ameliorates the Cognitive Deficit in Alzheimer's Disease Mouse Model through Macroautophagy and Chaperone-Mediated Autophagy Pathways.
J Agric Food Chem. 2021 Mar 3;69(8):2422-2437. doi: 10.1021/acs.jafc.0c07327. Epub 2021 Feb 22.
4
Relevance of Autophagy and Mitophagy Dynamics and Markers in Neurodegenerative Diseases.
Biomedicines. 2021 Feb 4;9(2):149. doi: 10.3390/biomedicines9020149.
5
Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies.
Open Biol. 2020 Dec;10(12):200286. doi: 10.1098/rsob.200286. Epub 2020 Dec 23.
6
FUNDC1 interacts with FBXL2 to govern mitochondrial integrity and cardiac function through an IP3R3-dependent manner in obesity.
Sci Adv. 2020 Sep 16;6(38). doi: 10.1126/sciadv.abc8561. Print 2020 Sep.
7
Noncanonical function of an autophagy protein prevents spontaneous Alzheimer's disease.
Sci Adv. 2020 Aug 14;6(33):eabb9036. doi: 10.1126/sciadv.abb9036. eCollection 2020 Aug.
8
Lactulose and Melibiose Attenuate MPTP-Induced Parkinson's Disease in Mice by Inhibition of Oxidative Stress, Reduction of Neuroinflammation and Up-Regulation of Autophagy.
Front Aging Neurosci. 2020 Jul 24;12:226. doi: 10.3389/fnagi.2020.00226. eCollection 2020.
9
Estrogen Exerts Neuroprotective Effects in Vascular Dementia Rats by Suppressing Autophagy and Activating the Wnt/β-Catenin Signaling Pathway.
Neurochem Res. 2020 Sep;45(9):2100-2112. doi: 10.1007/s11064-020-03072-5. Epub 2020 Jul 27.
10
Mitophagy Receptors and Mediators: Therapeutic Targets in the Management of Cardiovascular Ageing.
Ageing Res Rev. 2020 Sep;62:101129. doi: 10.1016/j.arr.2020.101129. Epub 2020 Jul 22.
Zotero 插件