Modulating mitochondrial calcium channels (TRPM2/MCU/NCX) as a therapeutic strategy for neurodegenerative disorders

Frontiers in Neuroscience

Neuroscience

Dorota L. Stankowska¹  Gretchen A. Johnson¹  Raghu R. Krishnamoorthy² 

[1] North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, United States;Department of Microbiology, Immunology and Genetics, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, United States;North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, United States;Department of Pharmacology and Neuroscience, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX, United States;

关键词: neurodegeneration;    mitochondria;    aging;    ROS;    calcium;   

DOI  :  10.3389/fnins.2023.1202167

 received in 2023-04-07, accepted in 2023-10-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

Efficient cellular communication is essential for the brain to regulate diverse functions like muscle contractions, memory formation and recall, decision-making, and task execution. This communication is facilitated by rapid signaling through electrical and chemical messengers, including voltage-gated ion channels and neurotransmitters. These messengers elicit broad responses by propagating action potentials and mediating synaptic transmission. Calcium influx and efflux are essential for releasing neurotransmitters and regulating synaptic transmission. Mitochondria, which are involved in oxidative phosphorylation, and the energy generation process, also interact with the endoplasmic reticulum to store and regulate cytoplasmic calcium levels. The number, morphology, and distribution of mitochondria in different cell types vary based on energy demands. Mitochondrial damage can cause excess reactive oxygen species (ROS) generation. Mitophagy is a selective process that targets and degrades damaged mitochondria via autophagosome-lysosome fusion. Defects in mitophagy can lead to a buildup of ROS and cell death. Numerous studies have attempted to characterize the relationship between mitochondrial dysfunction and calcium dysregulation in neurodegenerative diseases such as Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, Amyotrophic lateral sclerosis, spinocerebellar ataxia, and aging. Interventional strategies to reduce mitochondrial damage and accumulation could serve as a therapeutic target, but further research is needed to unravel this potential. This review offers an overview of calcium signaling related to mitochondria in various neuronal cells. It critically examines recent findings, exploring the potential roles that mitochondrial dysfunction might play in multiple neurodegenerative diseases and aging. Furthermore, the review identifies existing gaps in knowledge to guide the direction of future research.

【 授权许可】

Unknown   
Copyright © 2023 Johnson, Krishnamoorthy and Stankowska.