HMGB1-Mediated Neuroinflammatory Responses in Brain Injuries: Potential Mechanisms and Therapeutic Opportunities

Brain injuries are devastating conditions, representing a global cause of mortality and morbidity, with no effective treatment to date. Increased evidence supports the role of neuroinflammation in driving several forms of brain injuries. High mobility group box 1 (HMGB1) protein is a pro-inflammator...

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Veröffentlicht in:International journal of molecular sciences 2020-06, Vol.21 (13), p.4609
Hauptverfasser: Paudel, Yam Nath, Angelopoulou, Efthalia, Piperi, Christina, Othman, Iekhsan, Shaikh, Mohd Farooq
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container_title International journal of molecular sciences
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creator Paudel, Yam Nath
Angelopoulou, Efthalia
Piperi, Christina
Othman, Iekhsan
Shaikh, Mohd Farooq
description Brain injuries are devastating conditions, representing a global cause of mortality and morbidity, with no effective treatment to date. Increased evidence supports the role of neuroinflammation in driving several forms of brain injuries. High mobility group box 1 (HMGB1) protein is a pro-inflammatory-like cytokine with an initiator role in neuroinflammation that has been implicated in Traumatic brain injury (TBI) as well as in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Herein, we discuss the implication of HMGB1-induced neuroinflammatory responses in these brain injuries, mediated through binding to the receptor for advanced glycation end products (RAGE), toll-like receptor4 (TLR4) and other inflammatory mediators. Moreover, we provide evidence on the biomarker potential of HMGB1 and the significance of its nucleocytoplasmic translocation during brain injuries along with the promising neuroprotective effects observed upon HMGB1 inhibition/neutralization in TBI and EBI induced by SAH. Overall, this review addresses the current advances on neuroinflammation driven by HMGB1 in brain injuries indicating a future treatment opportunity that may overcome current therapeutic gaps.
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subjects Advanced glycosylation end products
Animals
Apoptosis
Brain Injuries - metabolism
Brain Injuries - pathology
Brain Injuries, Traumatic - metabolism
Brain Injuries, Traumatic - pathology
Brain research
Cell adhesion & migration
Cytokines
Cytokines - metabolism
Edema
Glycosylation
Hemorrhage
High mobility group proteins
HMGB1 protein
HMGB1 Protein - metabolism
Humans
Inflammation
Inflammation - metabolism
Kinases
Microglia - metabolism
Morbidity
Mortality
Neuroimmunomodulation
Neuroprotection
Neuroprotective Agents - pharmacology
Pediatrics
Proteins
Receptor for Advanced Glycation End Products - metabolism
Review
Signal Transduction
Subarachnoid hemorrhage
Subarachnoid Hemorrhage - metabolism
Subarachnoid Hemorrhage - pathology
TLR4 protein
Toll-Like Receptor 4 - metabolism
Toll-like receptors
Traumatic brain injury
title HMGB1-Mediated Neuroinflammatory Responses in Brain Injuries: Potential Mechanisms and Therapeutic Opportunities
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