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Cited by 87Genomics, phytochemicals, and oxidative stressEndoplasmic Reticulum Stress and DiseaseNuclear Receptors and Signaling

The NRF2 transcriptional target, OSGIN1, contributes to monomethyl fumarate-mediated cytoprotection in human astrocytes

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Brennan, Melanie S., Matos, Maria F., Richter, Karl E., Li, Bing, Scannevin, Robert H.·2017·Scientific Reports
DOI 10.1038/srep42054PMC PMC5299414
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Abstract

Dimethyl fumarate (DMF) is indicated for the treatment of relapsing multiple sclerosis and may exert therapeutic effects via activation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2) pathway. Following oral DMF administration, central nervous system (CNS) tissue is predominantly exposed to monomethyl fumarate (MMF), the bioactive metabolite of DMF, which can stabilize NRF2 and induce antioxidant gene expression; however, the detailed NRF2-dependent mechanisms modulated by MMF that lead to cytoprotection are unknown. Our data identify a mechanism for MMF-mediated cytoprotection in human astrocytes that functions in an OSGIN1-dependent manner, specifically via upregulation of the OSGIN1-61 kDa isoform. NRF2-dependent OSGIN1 expression induced P53 nuclear translocation following MMF administration, leading to cell-cycle inhibition and cell protection against oxidative challenge. This study provides mechanistic insight into MMF-mediated cytoprotection via NRF2, OSGIN1, and P53 in human CNS-derived cells and contributes to our understanding of how DMF may act clinically to ameliorate pathological processes in neurodegenerative disease.

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Cited by

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Authors
Brennan, M. S., Matos, M. F., Richter, K. E., Li, B., & Scannevin, R. H.
Affiliations
  • Boston University (US)
  • Biogen (United States) (US)
Corresponding author
Brennan, Melanie S.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-02-09
Volume
7
Issue
1
Pages
42054-42054
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep42054
PMC
PMC5299414
OpenAlex
W2586634345
Cited by
87
References
1
Citations by year
2026: 8 · 2025: 10 · 2024: 19 · 2023: 10 · 2022: 9 · 2021: 8 · 2020: 4 · 2019: 7 · 2018: 6 · 2017: 6
FWCI
2.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
School of Medicine, Boston University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
monomethyl fumarate, dimethyl fumarate, Nrf2, astrocytes, cytoprotection, p53 nuclear translocation, cell cycle arrest, oxidative stress, multiple sclerosis, neuroprotection, antioxidant response
MeSH terms
Astrocytes, Cells, Cultured, Fumarates, Humans, Proteins, Cytoprotection, Apoptosis Regulatory Proteins, NF-E2-Related Factor 2

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