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miRNA-Mediated Regulation of Ferroptosis in Neurological Disorders: Mechanisms and Therapeutic Implications
Chenyu Wang1, Tingrui Luo1, Nanhao Zhou1
1Health Science Center, Ningbo University, Ningbo 315211, China.
Abstract:
Ferroptosis is a form of regulated cell death driven by iron-dependent phospholipid peroxidation and has emerged as a key mechanism of neuronal injury across a broad spectrum of neurological disorders. MicroRNAs (miRNAs), which function primarily as post-transcriptional regulators of gene expression, are increasingly recognized as important modulators of the regulatory networks governing ferroptosis and as potential therapeutic targets in these conditions. In this review, we synthesize current advances in miRNA-mediated regulation of ferroptosis in neurological disorders. We first outline the core molecular pathways governing ferroptosis, with particular emphasis on antioxidant defense, lipid peroxidation, and iron metabolism. We then integrate evidence from ischemic stroke, intracerebral hemorrhage, epilepsy, toxic encephalopathy, spinal cord injury, Parkinson's disease, and Alzheimer's disease, to illustrate how disease-specific miRNA regulatory axes shape ferroptotic vulnerability and its pathological consequences in distinct neurological settings. Importantly, we highlight exosome-based strategies targeting ferroptosis-related miRNA networks as a promising therapeutic approach for neurological disorders, with demonstrated neuroprotective and functional benefits in preclinical studies. Collectively, current evidence supports miRNA-mediated regulation of ferroptosis as an important mechanistic framework and a promising therapeutic target in neurological disorders.
Insights
MicroRNAs (miRNAs) regulate ferroptosis, a cell death pathway causing neuronal injury in neurological disorders. Targeting these miRNA networks offers a promising neuroprotective therapy for conditions like stroke and Parkinson's disease.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Ferroptosis, an iron-dependent cell death, drives neuronal injury in diverse neurological disorders.
- MicroRNAs (miRNAs) are key post-transcriptional regulators influencing ferroptosis pathways.
- Dysregulation of miRNA-mediated ferroptosis contributes to neurological disease pathology.
Purpose of the Study:
- To review current understanding of miRNA-mediated ferroptosis in neurological disorders.
- To explore the role of miRNAs in ferroptosis across various neurological conditions.
- To highlight therapeutic strategies targeting miRNA-ferroptosis interactions.
Main Methods:
- Literature review synthesizing research on ferroptosis and miRNAs in neurological diseases.
- Analysis of core molecular pathways of ferroptosis: antioxidant defense, lipid peroxidation, iron metabolism.
- Integration of evidence from stroke, epilepsy, Parkinson's, Alzheimer's, and other neurological conditions.
Main Results:
- miRNA regulatory networks significantly modulate ferroptotic vulnerability in neurological disorders.
- Disease-specific miRNA axes dictate pathological consequences of ferroptosis.
- Exosome-based strategies targeting miRNA networks show preclinical neuroprotection.
Conclusions:
- miRNA-mediated ferroptosis is a critical mechanistic framework in neurological disorders.
- Targeting ferroptosis-related miRNA networks presents a promising therapeutic avenue.
- Further research into miRNA-ferroptosis interactions could yield novel treatments for neurodegeneration.
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