Microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and MPP+-induced neurotoxicity in Parkinson’s disease

Chronic neuroinflammation is implicated in the pathogenesis of Parkinson’s disease (PD), one of the most common neurodegenerative diseases. Itaconate, an endogenous metabolite derived from the tricarboxylic acid cycle via immune‐responsive gene 1 activity, may mediate anti-inflammatory responses by...

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Autores principales: Xia, Ning, Madore, Victoria, Albalakhi, Ali, Lin, Sonia, Stimpson, Taylor, Xu, Yuehang, Schwarzschild, Michael A., Bakshi, Rachit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511514/
https://www.ncbi.nlm.nih.gov/pubmed/37730914
http://dx.doi.org/10.1038/s41598-023-42813-8
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author Xia, Ning
Madore, Victoria
Albalakhi, Ali
Lin, Sonia
Stimpson, Taylor
Xu, Yuehang
Schwarzschild, Michael A.
Bakshi, Rachit
author_facet Xia, Ning
Madore, Victoria
Albalakhi, Ali
Lin, Sonia
Stimpson, Taylor
Xu, Yuehang
Schwarzschild, Michael A.
Bakshi, Rachit
author_sort Xia, Ning
collection PubMed
description Chronic neuroinflammation is implicated in the pathogenesis of Parkinson’s disease (PD), one of the most common neurodegenerative diseases. Itaconate, an endogenous metabolite derived from the tricarboxylic acid cycle via immune‐responsive gene 1 activity, may mediate anti-inflammatory responses by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway. This study investigates the neuroprotective potential of 4-octyl itaconate (OI), a cell-permeable derivative of itaconate, in cellular models of PD. OI not only suppressed lipopolysaccharide-induced proinflammatory cascades of inducible nitric oxide synthase, cyclooxygenase-2, and cytokines release in mouse BV2 microglial cells but also activated the Nrf2 signaling pathway and its downstream targets in these cells. Conditioned medium derived from OI-treated BV2 cells protected against rotenone- and MPP(+)-induced neurotoxicity in Neuro 2A cells. Overall, our findings support the anti-inflammatory neuroprotective potential of OI in PD.
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spelling pubmed-105115142023-09-22 Microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and MPP+-induced neurotoxicity in Parkinson’s disease Xia, Ning Madore, Victoria Albalakhi, Ali Lin, Sonia Stimpson, Taylor Xu, Yuehang Schwarzschild, Michael A. Bakshi, Rachit Sci Rep Article Chronic neuroinflammation is implicated in the pathogenesis of Parkinson’s disease (PD), one of the most common neurodegenerative diseases. Itaconate, an endogenous metabolite derived from the tricarboxylic acid cycle via immune‐responsive gene 1 activity, may mediate anti-inflammatory responses by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway. This study investigates the neuroprotective potential of 4-octyl itaconate (OI), a cell-permeable derivative of itaconate, in cellular models of PD. OI not only suppressed lipopolysaccharide-induced proinflammatory cascades of inducible nitric oxide synthase, cyclooxygenase-2, and cytokines release in mouse BV2 microglial cells but also activated the Nrf2 signaling pathway and its downstream targets in these cells. Conditioned medium derived from OI-treated BV2 cells protected against rotenone- and MPP(+)-induced neurotoxicity in Neuro 2A cells. Overall, our findings support the anti-inflammatory neuroprotective potential of OI in PD. Nature Publishing Group UK 2023-09-20 /pmc/articles/PMC10511514/ /pubmed/37730914 http://dx.doi.org/10.1038/s41598-023-42813-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xia, Ning
Madore, Victoria
Albalakhi, Ali
Lin, Sonia
Stimpson, Taylor
Xu, Yuehang
Schwarzschild, Michael A.
Bakshi, Rachit
Microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and MPP+-induced neurotoxicity in Parkinson’s disease
title Microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and MPP+-induced neurotoxicity in Parkinson’s disease
title_full Microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and MPP+-induced neurotoxicity in Parkinson’s disease
title_fullStr Microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and MPP+-induced neurotoxicity in Parkinson’s disease
title_full_unstemmed Microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and MPP+-induced neurotoxicity in Parkinson’s disease
title_short Microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and MPP+-induced neurotoxicity in Parkinson’s disease
title_sort microglia-dependent neuroprotective effects of 4-octyl itaconate against rotenone-and mpp+-induced neurotoxicity in parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511514/
https://www.ncbi.nlm.nih.gov/pubmed/37730914
http://dx.doi.org/10.1038/s41598-023-42813-8
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