TY - JOUR
T1 - Mtdna maintenance and alterations in the pathogenesis of neurodegenerative diseases
AU - Shang, Dehao
AU - Huang, Minghao
AU - Wang, Biyao
AU - Yan, Xu
AU - Wu, Zhou
AU - Zhang, Xinwen
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (Grant No. 81700977 to X. Y.; Grant No. 81500858 to X. Z.) and the Japanese KAKENHI Grant No. 22K09927 (Grants-in-Aid for Scientific Research to Z.W.).
Publisher Copyright:
© 2023 Bentham Science Publishers.
PY - 2023
Y1 - 2023
N2 - Considerable evidence indicates that the semiautonomous organelles mitochondria play key roles in the progression of many neurodegenerative disorders. Mitochondrial DNA (mtDNA) encodes components of the OXPHOS complex but mutated mtDNA accumulates in cells with aging, which mirrors the increased prevalence of neurodegenerative diseases. This accumulation stems not only from the misreplication of mtDNA and the highly oxidative environment but also from defective mitophagy after fission. In this review, we focus on several pivotal mitochondrial proteins related to mtDNA maintenance (such as ATAD3A and TFAM), mtDNA alterations including mtDNA mutations, mtDNA elimination, and mtDNA release-activated inflammation to understand the crucial role played by mtDNA in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Our work outlines novel therapeutic strategies for targeting mtDNA.
AB - Considerable evidence indicates that the semiautonomous organelles mitochondria play key roles in the progression of many neurodegenerative disorders. Mitochondrial DNA (mtDNA) encodes components of the OXPHOS complex but mutated mtDNA accumulates in cells with aging, which mirrors the increased prevalence of neurodegenerative diseases. This accumulation stems not only from the misreplication of mtDNA and the highly oxidative environment but also from defective mitophagy after fission. In this review, we focus on several pivotal mitochondrial proteins related to mtDNA maintenance (such as ATAD3A and TFAM), mtDNA alterations including mtDNA mutations, mtDNA elimination, and mtDNA release-activated inflammation to understand the crucial role played by mtDNA in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Our work outlines novel therapeutic strategies for targeting mtDNA.
UR - http://www.scopus.com/inward/record.url?scp=85151042754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85151042754&partnerID=8YFLogxK
U2 - 10.2174/1570159X20666220810114644
DO - 10.2174/1570159X20666220810114644
M3 - Review article
C2 - 35950246
AN - SCOPUS:85151042754
SN - 1570-159X
VL - 21
SP - 578
EP - 598
JO - Current Neuropharmacology
JF - Current Neuropharmacology
IS - 3
ER -
