Apoptosis and Autophagy in the Pathogenesis of Acute Ischemic Stroke (Review of Literature)

Abstract

According to the World Health Organization, about 5 million people die every year from cerebrovascular disease. At the same time, the proportion of cerebral infarction, or ischemic stroke (IS), among forms of acute cerebrovascular accident reaches 80-85%. Despite the active study of biochemical and morphological changes leading to acute cerebrovascular ischemia, the problem of early diagnosis, prevention, as well as predicting the outcome of this disease is still relevant. There is no doubt that the interruption of the ischemic cascade at earlier stages can be accompanied by a greater effect of treatment. A timely and effective pharmacological intervention requires a clear understanding of the pathochemical and biological processes underlying acute ischemia at the molecular level. High mortality and disability accompanying acute IS, dictate the need to create new diagnostic and prognosis algorithms both in the acute period of IS, and in the recovery period. According to some authors, elucidation of the pathways that underlie the pathogenetic mechanisms acting in the penumbra are of great clinical interest for the development of new diagnostic and therapeutic strategies. Studying the mechanisms of apoptosis and autophagy of neurons in the dynamics of the acute period of IS, modulation of the autophagy process in the penumbra zone can contribute to the development of new methods for the diagnosis and treatment of acute IS. The review presents the results of the latest experimental studies on the role of apoptosis and autophagy in the development of acute cerebral ischemia and attempts to modulate these processes in order to influence the ischemic cascade. The review was based on sources from such international and national data bases as Scopus, Web of Science, Springer, RINC.

Identification of Molecular Biomarkers Associated With Stroke Progression Using WGCNA and SVM-RFE

“…The PI3K/Akt signaling pathway is involved in various cellular processes, and it has been proved that the activation of this pathway is related to the occurrence and development of angiogenesis. The negative regulation of angiogenesis promotes the genes of thrombosis, vascular permeability, and in ammation, protecting thus vascular function (Lugovaya et al,2020). On the one hand, RelA, NF-κ B/ Rel family plays an important role in the response to in ammation and immunity, which may constitute the regulatory signal of PI3K-AKT, and then regulate the pathway of apoptosis (Gao et al,2019).…”

“…On the one hand, RelA, NF-κ B/ Rel family plays an important role in the response to in ammation and immunity, which may constitute the regulatory signal of PI3K-AKT, and then regulate the pathway of apoptosis (Gao et al,2019). On the other hand, several studies have con rmed that drugs can improve stroke symptoms by regulating the PI3K/Akt pathway (Lugovaya et al,2020). A recent study has also reported that PI3K/Akt regulates apoptosis and that the activation of the PI3K/Akt pathway after stroke plays a protective role in neuronal apoptosis (An et al,2017).…”

p53 Inhibition Protects against Neuronal Ischemia/Reperfusion Injury by the p53/PRAS40/mTOR Pathway

“…In addition, p53 participates in the process of apoptosis after ischemic stroke [37]. It was previously reported that brain I/R injury correlates with neuronal apoptosis, which can be regulated by p53 [38].…”

Potential Molecular Target Prediction and Docking Verification of Hua‐Feng‐Dan in Stroke Based on Network Pharmacology

“…Activated caspase-8 synergistically cleaves and activates the caspase of downstream effector molecules, such as caspase-1, caspase-3, caspase-6, and caspase-7, and amplifies the apoptosis signal [24]. PI3K/Akt signaling pathway participates in various cellular processes, and the activation of the pathway has been revealed to be implicated in the occurrence and development of angiogenesis, which negatively modulates genes that promote thrombogenicity, vascular permeability, and inflammation, and thereby protects vascular function [25]. RelA, one of the nuclear transcription factor κB (NF-κB)/Rel families, plays an important role in inflammation and immune response, which may be a PI3K-AKT regulatory signal, which in turn regulates the apoptosis pathway [26].…”

“…On the other hand, multiple studies have confirmed that drugs can improve stroke symptoms by regulating the PI3K/Akt pathway [27]. Studies have also reported that PI3K/Akt regulates cell apoptosis, and activation of the PI3K/Akt pathway after stroke plays a protective role in neuronal apoptosis [25]. Under pathological conditions of stroke, p53 plays an important role in the regulation of apoptosis and cell cycle [28].…”