中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (7): 1486-1488.doi: 10.4103/1673-5374.360279

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

改变新陈代谢以延长寿命

  

  1. 神经科学和细胞生物学中心,创新生物医学和生物技术中心,科英布拉大学,葡萄牙
  • 出版日期:2023-07-15 发布日期:2023-01-11

Overcoming mitochondrial dysfunction in neurodegenerative diseases

João Pessoa*, Ana I. Duarte   

  1. CNC – Center for Neuroscience and Cell Biology, CIBB – Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal
  • Online:2023-07-15 Published:2023-01-11
  • Contact: João Pessoa, PhD, joao.pessoa@cnc.uc.pt.
  • Supported by:
    This work was financed by the European Regional Development Fund (ERDF), through the COMPETE 2020 – Operational Programme for Competitiveness and Internationalization, under the project POCI-01-0145-FEDER-029391 (Mito4ALS); by Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia, under the projects UIDB/04539/2020, UIDP/04539/2020, LA/P/0058/2020, and UIDB/00081/2020; and by the European Social Fund, through the DL57/2016 - SFRH/BPD/84473/2012 to AID. 

摘要: https://orcid.org/0000-0002-9202-5728 (João Pessoa)

Abstract: Due to their intense electrical activity, neurons have high energy demands. This requirement makes them particularly sensitive to mitochondrial dysfunction. Like all eukaryotic cells, neurons have intrinsic mechanisms to mitigate the impact of mitochondrial dysfunction and its consequent production of toxic substances. Among such (neuro)protective mechanisms, mitochondrial autophagy (mitophagy) is responsible for the removal of dysfunctional mitochondria. Pathological inhibition of mitophagy, together with insufficient mitochondrial activity, results in a shortage of adenosine triphosphate (ATP) and the accumulation of reactive oxygen species (ROS) (Simmons et al., 2020). These alterations may trigger extensive apoptotic neuronal death (Figure 1A) which, together with the post-mitotic nature of neurons, impedes the replacement of the apoptotic cells. This irreversible loss of neurons may underlie the progressive decline in the function of the central nervous system, culminating in the arousal of neurodegenerative diseases (Simmons et al., 2020). The actual role of mitochondrial dysfunction has been increasingly demonstrated in Alzheimer’s disease. For example, post-mortem analysis of patient brains has revealed the reduced expression and activity of mitochondrial respiratory chain complexes (Troutwine et al., 2022).