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Grant support

This work was supported by the Spanish Ministry of Economy and Competitiveness (Grants Refs. SAF2016-76520-R to ILB and BFU2016-75973-R to MDG).

Analysis of institutional authors

Galan-Ganga, MAuthor

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Article

Cannabinoid CB2 Receptor Modulation by the Transcription Factor NRF2 is Specific in Microglial Cells

Publicated to:Cellular And Molecular Neurobiology. 40 (1): 167-177 - 2020-01-01 40(1), DOI: 10.1007/s10571-019-00719-y

Authors: Galan-Ganga, M; Del Rio, R; Jimenez-Moreno, N; Diaz-Guerra, M; Lastres-Becker, I

Affiliations

UAM, CSIC, Inst Invest Biomed Alberto Sols, Madrid, Spain - Author
UAM, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Inst Invest Sanitaria La Paz IdiPaz, Inst Invest Biomed Alberto Sols,CSIC, C Arturo Duperier 4, Madrid 28029, Spain - Author
Univ Autonoma Madrid, Sch Med, Dept Biochem, Madrid, Spain - Author
Univ Bristol, Sch Biochem, Med Sci Bldg, Bristol, Avon, England - Author

Abstract

Nuclear factor erythroid 2-related factor 2 (NRF2) is a pleiotropic transcription factor that has neuroprotective and anti-inflammatory effects, regulating more than 250 genes. As NRF2, cannabinoid receptor type 2 (CB2) is also implicated in the preservation of neurons against glia-driven inflammation. To this concern, little is known about the regulation pathways implicated in CB2 receptor expression. In this study, we analyze whether NRF2 could modulate the transcription of CB2 in neuronal and microglial cells. Bioinformatics analysis revealed an antioxidant response element in the promoter sequence of the CB2 receptor gene. Further analysis by chemical and genetic manipulations of this transcription factor demonstrated that NRF2 is not able to modulate the expression of CB2 in neurons. On the other hand, at the level of microglia, the expression of CB2 is NRF2-dependent. These results are related to the differential levels of expression of both genes regarding the brain cell type. Since modulation of CB2 receptor signaling may represent a promising therapeutic target with minimal psychotropic effects that can be used to modulate endocannabinoid-based therapeutic approaches and to reduce neurodegeneration, our findings will contribute to disclose the potential of CB2 as a novel target for treating different pathologies.

Keywords

ActivatioAnimalsAntioxidantAntioxidant response elementsBindingBrainCb2 receptorDeficiencyDimethyl fumarate (dmfDimethyl fumarate (dmf)ExpressionHumansInflammationMiceMicrogliaMouse modelNeuronNeuronsNf-e2-related factor 2Nf-kappa-bNrf2Promoter regions, geneticRats, wistarReceptor, cannabinoid, cb2Redox balanceTherapeutic target

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cellular And Molecular Neurobiology due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous).

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 5.93, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-26, the following number of citations:

  • WoS: 32
  • Scopus: 32
  • Europe PMC: 29
  • OpenCitations: 33

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 2025-06-26:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 42.
  • 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: 42 (PlumX).

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

  • The Total Score from Altmetric: 10.9.
  • The number of mentions on the social network Facebook: 1 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 19 (Altmetric).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United Kingdom.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Galán Ganga, Marcos) .