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阿尔茨海默病中的线粒体机制:治疗探索。

Mitochondrial mechanisms in Alzheimer's disease: Quest for therapeutics.

机构信息

Department of Chemistry, The University of Texas at San Antonio, San Antonio 78249, TX, USA; Regulatory Scientist, Vestaron Cooperation, Durham 27703, NC, USA.

Department of Physiotherapy, Lovely Professional University, Phagwara 144402, Punjab, India.

出版信息

Drug Discov Today. 2023 May;28(5):103547. doi: 10.1016/j.drudis.2023.103547. Epub 2023 Mar 5.


DOI:10.1016/j.drudis.2023.103547
PMID:36871845
Abstract

Mitochondrial function is essential for maintaining neuronal integrity, because neurons have a high energy demand. Neurodegenerative diseases, such as Alzheimer's disease (AD), are exacerbated by mitochondrial dysfunction. Mitochondrial autophagy (mitophagy) attenuates neurodegenerative diseases by eradicating dysfunctional mitochondria. In neurodegenerative disorders, there is disruption of the mitophagy process. High levels of iron also interfere with the mitophagy process and the mtDNA released after mitophagy is proinflammatory and triggers the cGAS-STING pathway that aids AD pathology. In this review, we critically discuss the factors that affect mitochondrial impairment and different mitophagy processes in AD. Furthermore, we discuss the molecules used in mouse studies as well as clinical trials that could result in potential therapeutics in the future.

摘要

线粒体功能对于维持神经元完整性至关重要,因为神经元的能量需求很高。神经退行性疾病,如阿尔茨海默病(AD),会因线粒体功能障碍而加重。线粒体自噬(mitophagy)通过消除功能失调的线粒体来减轻神经退行性疾病。在神经退行性疾病中,自噬过程会受到破坏。高水平的铁也会干扰自噬过程,自噬后释放的 mtDNA 具有炎症性,并触发 cGAS-STING 途径,从而促进 AD 病理。在这篇综述中,我们批判性地讨论了影响 AD 中线粒体损伤和不同自噬过程的因素。此外,我们还讨论了在小鼠研究和临床试验中使用的分子,这些分子可能会为未来的潜在治疗方法提供依据。

相似文献

[1]
Mitochondrial mechanisms in Alzheimer's disease: Quest for therapeutics.

Drug Discov Today. 2023-5

[2]
Mitophagy and Alzheimer's Disease: Cellular and Molecular Mechanisms.

Trends Neurosci. 2017-3

[3]
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CNS Neurol Disord Drug Targets. 2024

[4]
PINK1 Activation Attenuates Impaired Neuronal-Like Differentiation and Synaptogenesis and Mitochondrial Dysfunction in Alzheimer's Disease Trans-Mitochondrial Cybrid Cells.

J Alzheimers Dis. 2021

[5]
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[6]
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[7]
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[8]
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Neurosci Biobehav Rev. 2022-11

[9]
Role of mitophagy in mitochondrial quality control: Mechanisms and potential implications for neurodegenerative diseases.

Pharmacol Res. 2021-3

[10]
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引用本文的文献

[1]
Potential common pathogenesis of several neurodegenerative diseases.

Neural Regen Res. 2026-3-1

[2]
The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer's disease.

Mol Neurodegener. 2025-3-4

[3]
The cGAS-STING-related signature affects the prognosis of colorectal cancer through its regulation of multiple immune cells.

IUBMB Life. 2025-3

[4]
A promising drug repurposing approach for Alzheimer's treatment: Givinostat improves cognitive behavior and pathological features in APP/PS1 mice.

Redox Biol. 2024-12

[5]
MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.

Neurochem Res. 2024-10

[6]
Mushroom-derived bioactive components with definite structures in alleviating the pathogenesis of Alzheimer's disease.

Front Pharmacol. 2024-5-21

[7]
Impact of Donepezil Supplementation on Alzheimer's Disease-like Pathology and Gut Microbiome in APP/PS1 Mice.

Microorganisms. 2023-9-13

[8]
Repurposing of Tibolone in Alzheimer's Disease.

Biomolecules. 2023-7-13

[9]
Mapping trends and hotspots of mitochondrial dysfunction in Alzheimer's disease from 2013 to 2022: a bibliometric analysis of global research.

Front Neurosci. 2023-6-26

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