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García-Merino A.Author

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December 23, 2024
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Neuroprotective and Anti-Inflammatory Effects of Dimethyl Fumarate, Monomethyl Fumarate, and Cannabidiol in Neurons and Microglia

Publicated to: International Journal Of Molecular Sciences. 25 (23): 13082- - 2024-12-01 25(23), DOI: 10.3390/ijms252313082

Authors:

Sanchez-Sanz, A; Garcia-Merino, A; Sanchez-Lopez, AJ; Coronado-Albi, MJ; Munoz-Viana, R
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Affiliations

Bioinformatics Unit, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain. - Author
Confocal Microscopy Core Facility, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain. - Author
Neuroimmunology Unit, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain. - Author
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Abstract

Dimethyl fumarate (DMF) is an immunomodulatory treatment for multiple sclerosis (MS) that can cross the blood-brain barrier, presenting neuroprotective potential. Its mechanism of action is not fully understood, and there is a need to characterize whether DMF or its bioactive metabolite monomethyl fumarate (MMF) exerts neuroprotective properties. Moreover, the combination of adjuvant agents such as cannabidiol (CBD) could be relevant to enhance neuroprotection. The aim of this study was to compare the neuroprotective and immunomodulatory effects of DMF, MMF, and CBD in neurons and microglia in vitro. We found that DMF and CBD, but not MMF, activated the Nrf2 antioxidant pathway in neurons. Similarly, only DMF and CBD, but not MMF, prevented the LPS-induced activation of the inflammatory pathway NF-kB in microglia. Additionally, the three drugs inhibited the production of nitric oxide in microglia and protected neurons against apoptosis. Transcriptomically, DMF modulated a greater number of inflammatory and Nrf2-related genes compared to MMF and CBD in both neurons and microglia. Our results show that DMF and MMF, despite being structurally related, present differences in their mechanisms of action that could be relevant for the achievement of neuroprotection in MS patients. Additionally, CBD shows potential as a neuroprotective agent.
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Keywords

Acid estersActivationAnimalsAnti-inflammatory agentsAntioxidantApoptosisCannabidiolCellsCells, culturedDimethyl fumarateFumaratesGlutathioneHumansLipopolysaccharidesMiceMicrogliaMonomethyl fumarateMultiple sclerosisMultiple-sclerosisNeuronNeuronsNeuroprotectionNeuroprotective agentsNf-e2-related factor 2Nf-kNf-kappa bNf-kappa-bNf-kbNitric oxideNrf2PathwaRatsTranscriptionTranscriptome

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal International Journal Of Molecular Sciences due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 72/320, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-01-02:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 12 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

    It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

    • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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    Awards linked to the item

    This research was funded by the Instituto de Salud Carlos III (ISCIII) through the projects PI15/02099 and PI18/01766, co-funded by the European Regional Development Fund "A way to make Europe". A.S.-S. is a recipient of the PFIS predoctoral fellowship FI19/00149 by ISCIII, co-funded by the European Social Fund "Investing in your future".
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