A comprehensive review of stroke-related signaling pathways and treatment in western medicine and traditional Chinese medicine

Abstract

This review provides insight into the complex network of signaling pathways and mechanisms involved in stroke pathophysiology. It summarizes the historical progress of stroke-related signaling pathways, identifying potential interactions between them and emphasizing that stroke is a complex network disease. Of particular interest are the Hippo signaling pathway and ferroptosis signaling pathway, which remain understudied areas of research, and are therefore a focus of the review. The involvement of multiple signaling pathways, including Sonic Hedgehog (SHH), nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE), hypoxia-inducible factor-1α (HIF-1α), PI3K/AKT, JAK/STAT, and AMPK in pathophysiological mechanisms such as oxidative stress and apoptosis, highlights the complexity of stroke. The review also delves into the details of traditional Chinese medicine (TCM) therapies such as Rehmanniae and Astragalus, providing an analysis of the recent status of western medicine in the treatment of stroke and the advantages and disadvantages of TCM and western medicine in stroke treatment. The review proposes that since stroke is a network disease, TCM has the potential and advantages of a multi-target and multi-pathway mechanism of action in the treatment of stroke. Therefore, it is suggested that future research should explore more treasures of TCM and develop new therapies from the perspective of stroke as a network disease.

Molecular subtype identification of cerebral ischemic stroke based on ferroptosis-related genes

“…At the cellular level, hypoperfusion, hypoxia, and glucose deficiency cause insufficient energy production in brain metabolism, thus leading to some toxic metabolites accumulating locally, such as excitatory toxic products, acidic metabolites, oxidative stress products, and inflammatory mediators, resulting in cerebral cell dysfunction or death 45 . Various pathophysiological mechanisms had been reported to be involved in stroke, including angiogenesis, oxidative stress, autophagy formation, inflammatory response, and apoptosis 46 .…”

Is Autism a PIN1 Deficiency Syndrome? A Proposed Etiological Role for Glyphosate

“…DAPK1 phosphorylates p53 at Ser23 by direct binding of DD at the p53 DNA binding domain. Phosphorylation of p53 Ser23 by DAPK1 induces the transcriptional activation of BAX, whereas in the cytoplasm it induces mitochondrial associated necrosis and apoptosis, as indicated in studies on neurons [191][192][193][194]. Moreover, an indirect regulation of p53 by DAPK1 is through DAPK1's direct binding to MDM2 and its phosphorylation at Thr-419.…”

Recent advances in potential therapeutic targets of ferroptosis‑associated pathways for the treatment of stroke (Review)

“…Through clinical trial studies, TCM combined with the influencing factors associated with ferroptosis has been shown to be more effective than single-drug treatment for stroke ( 177 , 178 ). It is well established that TCM herbs have antioxidant, anti-inflammatory and blood-brain barrier-protective effects, and that they can prevent stroke in advance by various means ( 179 – 181 ).…”

“…In addition, the intervention of Chinese medicines on ferroptosis has been shown to be more stable and safer to use compared with small-molecule inducers or inhibitors of ferroptosis ( 185 ). For example, astragaloside IV can alleviate brain injury by inhibiting the ferroptosis-associated sequestosome-1/kelch-like ECH associated protein 1/nuclear factor erythroid 2-related factor 2 pathway ( 177 , 186 ). In addition, there are studies reporting that TCM treatment can reduce the side effects of drug toxicity in patients via targeting ferroptosis, leading to significant improvements in patient safety and quality of life ( 187 , 188 ).…”