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Updated: Jul 9, 2025
Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke
Published on: January 3, 2025
Regulated necrosis pathways: a potential target for ischemic stroke
Kaidi Ren1,2,3, Jinyan Pei4, Yuanyuan Guo1,2,3
1Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Dong Road, ErQi District, Zhengzhou 450052, China.
Abstract:
Globally, ischemic stroke causes millions of deaths per year. The outcomes of ischemic stroke are largely determined by the amount of ischemia-related and reperfusion-related neuronal death in the infarct region. In the infarct region, cell injuries follow either the regulated pathway involving precise signaling cascades, such as apoptosis and autophagy, or the nonregulated pathway, which is uncontrolled by any molecularly defined effector mechanisms such as necrosis. However, numerous studies have recently found that a certain type of necrosis can be regulated and potentially modified by drugs and is nonapoptotic; this type of necrosis is referred to as regulated necrosis. Depending on the signaling pathway, various elements of regulated necrosis contribute to the development of ischemic stroke, such as necroptosis, pyroptosis, ferroptosis, pathanatos, mitochondrial permeability transition pore-mediated necrosis and oncosis. In this review, we aim to summarize the underlying molecular mechanisms of regulated necrosis in ischemic stroke and explore the crosstalk and interplay among the diverse types of regulated necrosis. We believe that targeting these regulated necrosis pathways both pharmacologically and genetically in ischemia-induced neuronal death and protection could be an efficient strategy to increase neuronal survival and regeneration in ischemic stroke.
Insights
Ischemic stroke causes significant neuronal death via regulated necrosis pathways like necroptosis and ferroptosis. Targeting these pathways offers a promising strategy for neuronal survival and regeneration in stroke patients.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Ischemic stroke is a leading cause of death globally, with outcomes heavily influenced by neuronal death in the infarct region.
- Neuronal injury in stroke occurs through regulated pathways (apoptosis, autophagy) and non-regulated necrosis.
- Regulated necrosis, a non-apoptotic cell death pathway, is increasingly recognized for its role in ischemic stroke.
Purpose of the Study:
- To review the molecular mechanisms of various regulated necrosis pathways in ischemic stroke.
- To explore the interactions and crosstalk among different regulated necrosis types.
- To highlight the therapeutic potential of targeting regulated necrosis for stroke treatment.
Main Methods:
- Literature review of studies on regulated necrosis in ischemic stroke.
- Analysis of molecular signaling cascades involved in cell death pathways.
- Examination of preclinical and clinical data on targeting regulated necrosis.
Main Results:
- Identified key regulated necrosis pathways including necroptosis, pyroptosis, ferroptosis, and others.
- Detailed the molecular mechanisms and signaling crosstalk among these pathways.
- Demonstrated the contribution of regulated necrosis to ischemia- and reperfusion-induced neuronal injury.
Conclusions:
- Regulated necrosis pathways are critical contributors to neuronal death in ischemic stroke.
- Understanding the interplay between these pathways is essential for developing effective therapies.
- Targeting regulated necrosis pharmacologically or genetically presents a viable strategy for enhancing neuronal survival and promoting regeneration after stroke.
