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Translational Stroke Research

11-03-2024 | Stroke | Review

Type I Interferon Signalling and Ischemic Stroke: Mechanisms and Therapeutic Potentials

Authors: Pan Cui, Bo Song, Zongping Xia, Yuming Xu

Published in: Translational Stroke Research

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Abstract

Type I interferon (IFN-I) signalling is intricately involved in the pathogenesis of multiple infectious diseases, autoimmune diseases, and neurological diseases. Acute ischemic stroke provokes overactivation of IFN-I signalling within the injured brain, particularly in microglia. Following cerebral ischemia, damage-associated molecular patterns (DAMPs) released from injured neural cells elicit marked proinflammatory episodes within minutes. Among these, self-nucleic acids, including nuclear DNA and mitochondrial DNA (mtDNA), have been recognized as a critical alarm signal to fan the flames of neuroinflammation, predominantly via inducing IFN-I signalling activation in microglia. The concept of interferon-responsive microglia (IRM), marked by upregulation of a plethora of IFN-stimulated genes, has been emergingly elucidated in ischemic mouse brains, particularly in aged ones. Among the pattern recognition receptors responsible for IFN-I induction, cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) plays integral roles in potentiating microglia-driven neuroinflammation and secondary brain injury after cerebral ischemia. Here, we aim to provide an up-to-date review on the multifaceted roles of IFN-I signalling, the detailed molecular and cellular mechanisms leading to and resulting from aberrant IFN-I signalling activation after cerebral ischemia, and the therapeutic potentials. A thorough exploration of these above points will inform our quest for IFN-based therapies as effective immunomodulatory therapeutics to complement the limited repertoire of thrombolytic agents, thereby facilitating the translation from bench to bedside.
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Metadata
Title
Type I Interferon Signalling and Ischemic Stroke: Mechanisms and Therapeutic Potentials
Authors
Pan Cui
Bo Song
Zongping Xia
Yuming Xu
Publication date
11-03-2024
Publisher
Springer US
Published in
Translational Stroke Research
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-024-01236-x