Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases

Neuronal death is associated with mitochondrial dysfunction caused by mutations in mitochondrial DNA. Mitochondrial DNA becomes damaged when processes such as replication, repair, and nucleotide synthesis are compromised. This extensive accumulation of damaged mitochondrial DNA subsequently disrupts...

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Main Authors: Ye Hong, Ying Song, Wenjun Wang, Jinghui Shi, Xi Chen
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-07-01
Series:Genes and Diseases
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352304224002344
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author Ye Hong
Ying Song
Wenjun Wang
Jinghui Shi
Xi Chen
author_facet Ye Hong
Ying Song
Wenjun Wang
Jinghui Shi
Xi Chen
author_sort Ye Hong
collection DOAJ
description Neuronal death is associated with mitochondrial dysfunction caused by mutations in mitochondrial DNA. Mitochondrial DNA becomes damaged when processes such as replication, repair, and nucleotide synthesis are compromised. This extensive accumulation of damaged mitochondrial DNA subsequently disrupts the normal function of mitochondria, leading to aging, degeneration, or even death of neurons. Mitochondrial dysfunction stands as a pivotal factor in the development of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Recognizing the intricate nature of their pathogenesis, there is an urgent need for more effective therapeutic interventions. In recent years, mitochondrial DNA editing tools such as zinc finger nucleases, double-stranded DNA deaminase toxin A-derived cytosine base editors, and transcription activator-like effector ligand deaminases have emerged. Their emergence will revolutionize the research and treatment of mitochondrial diseases. In this review, we summarize the advancements in mitochondrial base editing technology and anticipate its utilization in neurodegenerative diseases, offering insights that may inform preventive strategies and therapeutic interventions for disease phenotypes.
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spelling doaj-art-35e3fa9d21cf4d26b8fb34e874fb49d42025-08-20T02:14:24ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-07-0112410143710.1016/j.gendis.2024.101437Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseasesYe Hong0Ying Song1Wenjun Wang2Jinghui Shi3Xi Chen4Department of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, ChinaDepartment of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China; Hangzhou King's Bio-pharmaceutical Technology Co., Ltd., Hangzhou, Zhejiang 310007, China; Corresponding author. Department of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.Department of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, ChinaDepartment of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, ChinaDepartment of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, ChinaNeuronal death is associated with mitochondrial dysfunction caused by mutations in mitochondrial DNA. Mitochondrial DNA becomes damaged when processes such as replication, repair, and nucleotide synthesis are compromised. This extensive accumulation of damaged mitochondrial DNA subsequently disrupts the normal function of mitochondria, leading to aging, degeneration, or even death of neurons. Mitochondrial dysfunction stands as a pivotal factor in the development of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Recognizing the intricate nature of their pathogenesis, there is an urgent need for more effective therapeutic interventions. In recent years, mitochondrial DNA editing tools such as zinc finger nucleases, double-stranded DNA deaminase toxin A-derived cytosine base editors, and transcription activator-like effector ligand deaminases have emerged. Their emergence will revolutionize the research and treatment of mitochondrial diseases. In this review, we summarize the advancements in mitochondrial base editing technology and anticipate its utilization in neurodegenerative diseases, offering insights that may inform preventive strategies and therapeutic interventions for disease phenotypes.http://www.sciencedirect.com/science/article/pii/S2352304224002344Base editorCRISPR-Cas9Mitochondrial DNAmitoTALENsmitoZFNsNeurodegenerative diseases
spellingShingle Ye Hong
Ying Song
Wenjun Wang
Jinghui Shi
Xi Chen
Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases
Genes and Diseases
Base editor
CRISPR-Cas9
Mitochondrial DNA
mitoTALENs
mitoZFNs
Neurodegenerative diseases
title Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases
title_full Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases
title_fullStr Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases
title_full_unstemmed Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases
title_short Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases
title_sort mitochondrial dna editing key to the treatment of neurodegenerative diseases
topic Base editor
CRISPR-Cas9
Mitochondrial DNA
mitoTALENs
mitoZFNs
Neurodegenerative diseases
url http://www.sciencedirect.com/science/article/pii/S2352304224002344
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