Tian, H.-Y.; Huang, B.-Y.; Nie, H.-F.; Chen, X.-Y.; Zhou, Y.; Yang, T.; Cheng, S.-W.; Mei, Z.-G.; Ge, J.-W. The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases. Brain Sci.2023, 13, 1367.
Tian, H.-Y.; Huang, B.-Y.; Nie, H.-F.; Chen, X.-Y.; Zhou, Y.; Yang, T.; Cheng, S.-W.; Mei, Z.-G.; Ge, J.-W. The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases. Brain Sci. 2023, 13, 1367.
Tian, H.-Y.; Huang, B.-Y.; Nie, H.-F.; Chen, X.-Y.; Zhou, Y.; Yang, T.; Cheng, S.-W.; Mei, Z.-G.; Ge, J.-W. The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases. Brain Sci.2023, 13, 1367.
Tian, H.-Y.; Huang, B.-Y.; Nie, H.-F.; Chen, X.-Y.; Zhou, Y.; Yang, T.; Cheng, S.-W.; Mei, Z.-G.; Ge, J.-W. The Interplay between Mitochondrial Dysfunction and Ferroptosis during Ischemia-Associated Central Nervous System Diseases. Brain Sci. 2023, 13, 1367.
Abstract
Cerebral ischemia, which is a leading cause of disability and mortality worldwide, sets off a chain of molecular and cellular pathologies that are associated with some central nervous system (CNS) disorders, mainly including ischemic stroke, Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy and other CNS diseases. In recent times, despite significant advancements in the treatment of the pathological processes underlying various neurological illnesses, effective therapeutic approaches specifically targeted at minimizing the damage of such diseases remain absent. Remarkably, ischemia causes severe damage to cells in Ischemia-associated CNS Diseases. Cerebral ischemia initiates oxygen and glucose deprivation, which subsequently promotes mitochondrial dysfunction, including MPTP opening, mitophagy dysfunction, and excessive mitochondrial fission, triggering various forms of cell death, such as autophagy, apoptosis, as well as ferroptosis. Ferroptosis, a novel type of regulated cell death (RCD), is characterized by iron-dependent accumulation of lethal reactive oxygen species and lipid peroxidation. Mitochondrial dysfunction and ferroptosis both play critical roles in the pathogenic progression of Ischemia-associated CNS Diseases. In recent years, growing evidence has indicated that mitochondrial dysfunction interplays with ferroptosis to aggravate cerebral ischemia injury. However, the potential connections between mitochondrial dysfunction and ferroptosis in Cerebral Ischemia have not yet been clarified. Thus, we analyze the underlying mechanism between mitochondrial dysfunction and ferroptosis in Ischemia-associated CNS Diseases. We also discovered that GSH depletion and GPX4 inactivation cause lipoxygenase activation and calcium influx following cerebral ischemia injury, resulting in MPTP opening and mitochondrial dysfunction. Additionally, dysfunction in mitochondrial electron transport and an imbalanced fusion-to-fission ratio can lead to the accumulation of reactive oxygen species and iron overload, which further contribute to the occurrence of ferroptosis. This creates a vicious cycle that continuously worsens cerebral ischemia injury. In this study, our focus is on exploring the interplay between mitochondrial dysfunction and ferroptosis, which may offer new insights into potential therapeutic approaches for the treatment of Ischemia-associated CNS Diseases.
Keywords
cerebral ischemia; central nervous system diseases; mitochondrial dysfunction, ferroptosis; therapeutics
Subject
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
