期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 37, 期 7-9, 页码 578-596出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2021.0152
关键词
bioenergetics; diabetic neuropathy; electron transport; laminopathy; mitochondrial respiration; superoxide
资金
- Canadian Institutes of Health Research [MOP-130282]
- Natural Sciences and Engineering Research Council of Canada [RGPIN-2019-05371]
This review discusses the significant role of ROS in the peripheral nervous system in the context of type 1 diabetes, highlighting the impact of hyperglycemia on driving ROS production and oxidative stress contributing to neurodegeneration. It also emphasizes the importance of understanding diabetes-induced changes in autophagy, ER function, and mitochondrial dysfunction for future research directions in diabetic neuropathy.
Significance: This review highlights the many intracellular processes generating reactive oxygen species (ROS) in the peripheral nervous system in the context of type 1 diabetes. The major sources of superoxide and hydrogen peroxide (H2O2) are described, and scavenging systems are explained. Important roles of ROS in regulating normal redox signaling and in a disease setting, such as diabetes, contributing to oxidative stress and cellular damage are outlined. The primary focus is the role of hyperglycemia in driving elevated ROS production and oxidative stress contributing to neurodegeneration in diabetic neuropathy (within the dorsal root ganglia [DRG] and peripheral nerve).Recent Advances: Contributors to ROS production under high intracellular glucose concentration such as mitochondria and the polyol pathway are discussed. The primarily damaging impact of ROS on multiple pathways including mitochondrial function, endoplasmic reticulum (ER) stress, autophagy, and epigenetic signaling is covered.Critical Issues: There is a strong focus on mechanisms of diabetes-induced mitochondrial dysfunction and how this may drive ROS production (in particular superoxide). The mitochondrial sites of superoxide/H2O2 production via mitochondrial metabolism and aerobic respiration are reviewed.Future Directions: Areas for future development are highlighted, including the need to clarify diabetes-induced changes in autophagy and ER function in neurons and Schwann cells. In addition, more clarity is needed regarding the sources of ROS production at mitochondrial sites under high glucose concentration (and lack of insulin signaling). New areas of study should be introduced to investigate the role of ROS, nuclear lamina function, and epigenetic signaling under diabetic conditions in peripheral nerve.
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