Mitochondrial Dynamics: A Potential Therapeutic Target for Ischemic Stroke

Abstract

Stroke is one of the leading causes of death and disability worldwide. Brain injury after ischemic stroke involves multiple pathophysiological mechanisms, such as oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium overload, neuroinflammation, neuronal apoptosis, and blood-brain barrier (BBB) disruption. All of these factors are associated with dysfunctional energy metabolism after stroke. Mitochondria are organelles that provide adenosine triphosphate (ATP) to the cell through oxidative phosphorylation. Mitochondrial dynamics means that the mitochondria are constantly changing and that they maintain the normal physiological functions of the cell through continuous division and fusion. Mitochondrial dynamics are closely associated with various pathophysiological mechanisms of post-stroke brain injury. In this review, we will discuss the role of the molecular mechanisms of mitochondrial dynamics in energy metabolism after ischemic stroke, as well as new strategies to restore energy homeostasis and neural function. Through this, we hope to uncover new therapeutic targets for the treatment of ischemic stroke.

[Retracted] Helicid Improves Lipopolysaccharide‐Induced Apoptosis of C6 Cells by Regulating SH2D5 DNA Methylation via the CytC/Caspase9/Caspase3 Signaling Pathway

“…Transient permeability can result in mitochondrial swelling, giving rise to rupture of the mitochondrial outer membrane and the release of cytochrome C, which triggers caspase activation. In the present study, overexpression of SH2D5 or treatment with helicid reversed the increased expression levels of Bax, CytC, and cleavage caspase3 and decreased Bcl-2 levels, indicating that SH2D5 or helicid has a strong antiapoptotic effect on central nervous system cell lines [ 33 , 34 ].…”

N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

“…Ischemic stroke results in neural death through complex pathophysiological pathways, including excitotoxicity [70], oxidative stress [71][72][73][74], blood-brain barrier disruption [75], and inflammation [76]. Based on the proposed role for NAAG in preventing excitotoxicity, a neuroprotective effect in stroke seems intuitive.…”

Network Pharmacology and Molecular Docking-Based Mechanism Study to Reveal the Protective Effect of Salvianolic Acid C in a Rat Model of Ischemic Stroke

“…And KEGG analysis revealed that pathways of SAC against IS include Proteoglycans in cancer, Pathways in cancer, Estrogen signaling pathway, Complement and coagulation cascades, Hypertrophic cardiomyopathy (HCM), HIF-1 signaling pathway, Focal adhesion, Arachidonic acid metabolism, PI3K-Akt signaling pathway, etc. It can be seen that these pathways are mainly related to anti-inflammatory, anti-apoptosis, anti-oxidant stress (Duronio, 2008;Huang et al, 2018;Liu et al, 2019) and other physiological and pathological processes, which are also closely related to the pathological process of IS (Zhou et al, 2021).…”

“…When IS occurs, due to the interruption of blood supply and the destruction of blood brain barrier (BBB), cells in the brain can't maintain normal physiological functions. Then neuron damage and death may occur in the presence of energy depletion, oxidative stress, excitotoxicity, inflammatory response and other pathological factors (Yang et al, 2018;Zhou et al, 2021). The therapeutic effect of existing drugs is not ideal (Ciccone et al, 2013;Saver et al, 2015).…”