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Electrophile Signaling and Emerging Immuno- and Neuro-modulatory Electrophilic Pharmaceuticals

With a lipid-rich environment and elevated oxygen consumption, the central nervous system (CNS) is subject to intricate regulation by lipid-derived electrophiles (LDEs). Investigations into oxidative damage and chronic LDE generation in neural disorders have spurred the development of tools that can...

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Autores principales: Poganik, Jesse R., Aye, Yimon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019031/
https://www.ncbi.nlm.nih.gov/pubmed/32116644
http://dx.doi.org/10.3389/fnagi.2020.00001
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author Poganik, Jesse R.
Aye, Yimon
author_facet Poganik, Jesse R.
Aye, Yimon
author_sort Poganik, Jesse R.
collection PubMed
description With a lipid-rich environment and elevated oxygen consumption, the central nervous system (CNS) is subject to intricate regulation by lipid-derived electrophiles (LDEs). Investigations into oxidative damage and chronic LDE generation in neural disorders have spurred the development of tools that can detect and catalog the gamut of LDE-adducted proteins. Despite these advances, deconstructing the precise consequences of individual protein-specific LDE modifications remained largely impossible until recently. In this perspective, we first overview emerging toolsets that can decode electrophile-signaling events in a protein/context-specific manner, and how the accumulating mechanistic insights brought about by these tools have begun to offer new means to modulate pathways relevant to multiple sclerosis (MS). By surveying the latest data surrounding the blockbuster MS drug dimethyl fumarate that functions through LDE-signaling-like mechanisms, we further provide a vision for how chemical biology tools probing electrophile signaling may be leveraged toward novel interventions in CNS disease.
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spelling pubmed-70190312020-02-28 Electrophile Signaling and Emerging Immuno- and Neuro-modulatory Electrophilic Pharmaceuticals Poganik, Jesse R. Aye, Yimon Front Aging Neurosci Neuroscience With a lipid-rich environment and elevated oxygen consumption, the central nervous system (CNS) is subject to intricate regulation by lipid-derived electrophiles (LDEs). Investigations into oxidative damage and chronic LDE generation in neural disorders have spurred the development of tools that can detect and catalog the gamut of LDE-adducted proteins. Despite these advances, deconstructing the precise consequences of individual protein-specific LDE modifications remained largely impossible until recently. In this perspective, we first overview emerging toolsets that can decode electrophile-signaling events in a protein/context-specific manner, and how the accumulating mechanistic insights brought about by these tools have begun to offer new means to modulate pathways relevant to multiple sclerosis (MS). By surveying the latest data surrounding the blockbuster MS drug dimethyl fumarate that functions through LDE-signaling-like mechanisms, we further provide a vision for how chemical biology tools probing electrophile signaling may be leveraged toward novel interventions in CNS disease. Frontiers Media S.A. 2020-02-07 /pmc/articles/PMC7019031/ /pubmed/32116644 http://dx.doi.org/10.3389/fnagi.2020.00001 Text en Copyright © 2020 Poganik and Aye. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Poganik, Jesse R.
Aye, Yimon
Electrophile Signaling and Emerging Immuno- and Neuro-modulatory Electrophilic Pharmaceuticals
title Electrophile Signaling and Emerging Immuno- and Neuro-modulatory Electrophilic Pharmaceuticals
title_full Electrophile Signaling and Emerging Immuno- and Neuro-modulatory Electrophilic Pharmaceuticals
title_fullStr Electrophile Signaling and Emerging Immuno- and Neuro-modulatory Electrophilic Pharmaceuticals
title_full_unstemmed Electrophile Signaling and Emerging Immuno- and Neuro-modulatory Electrophilic Pharmaceuticals
title_short Electrophile Signaling and Emerging Immuno- and Neuro-modulatory Electrophilic Pharmaceuticals
title_sort electrophile signaling and emerging immuno- and neuro-modulatory electrophilic pharmaceuticals
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019031/
https://www.ncbi.nlm.nih.gov/pubmed/32116644
http://dx.doi.org/10.3389/fnagi.2020.00001
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