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This work was supported by a Spanish Ministry of Economy and Competitiveness Grants refs. SAF2016-76520-R and PID2019-105600RB-I00 to ILB; Ref. RTI2018-095793-B-I00 to MGL. General Council for Research and Innovation of the Community of Madrid and European Structural Funds Ref. S2017/BMD-3813-ELA_Madrid to ILB and B2017/BMD-3827 - NRF24ADCM to MGL. Fundacion Tatiana Perez de Guzman el Bueno P-043-FTPGB 2020 to ILB.

Analysis of institutional authors

Galan-Ganga, MAuthor

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November 13, 2024
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Article

Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration

Publicated to:Acta Neuropathologica Communications. 9 (1): 90- - 2021-05-17 9(1), DOI: 10.1186/s40478-021-01196-5

Authors: Galan-Ganga, M; Rodriguez-Cueto, C; Merchan-Rubira, J; Hernandez, F; avila, J; Posada-Ayala, M; Lanciego, J L; Luengo, E; Lopez, M G; Rabano, A; Fernandez-Ruiz, J; Lastres-Becker, I

Affiliations

Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain - Author
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain - Author
Inst Salud Carlos III, Unidad Invest Proyecto Alzheimer, Fdn CIEN, Dept Neuropathol & Tissue Bank, Madrid, Spain - Author
Univ Autonoma Madrid UAM, Sch Med, Dept Biochem, Inst Invest Biomed Alberto Sols UAM CSIC,Inst Inv, C Arturo Duperier 4, Madrid 28029, Spain - Author
Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, UAM, Madrid, Spain - Author
Univ Autonoma Madrid, Fac Med, Dept Farmacol & Terapeut, Madrid 28029, Spain - Author
Univ Autonoma Madrid, Fac Med, Inst Teofilo Hernando, Madrid 28029, Spain - Author
Univ Complutense, Fac Med, Dept Bioquim & Biol Mol, Inst Univ Invest Neuroquim, Madrid, Spain - Author
Univ Francisco Vitoria, Fac Expt Sci, Madrid, Spain - Author
Univ Navarra, Ctr Appl Med Res, Dept Neurosci, Pio 12 Ave 55,Edificio CIMA, Pamplona 31008, Navarra, Spain - Author
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Abstract

Tauopathies are a group of neurodegenerative diseases characterized by the alteration/aggregation of TAU protein, for which there is still no effective treatment. Therefore, new pharmacological targets are being sought, such as elements of the endocannabinoid system (ECS). We analysed the occurrence of changes in the ECS in tauopathies and their implication in the pathogenesis. By integrating gene expression analysis, immunofluorescence, genetic and adeno-associated virus expressing TAU mouse models, we found a TAU-dependent increase in CB2 receptor expression in hippocampal neurons, that occurs as an early event in the pathology and was maintained until late stages. These changes were accompanied by alterations in the endocannabinoid metabolism. Remarkably, CB2 ablation in mice protects from neurodegeneration induced by hTAU(P301L) overexpression, corroborated at the level of cognitive behaviour, synaptic plasticity, and aggregates of insoluble TAU. At the level of neuroinflammation, the absence of CB2 did not produce significant changes in concordance with a possible neuronal location rather than its classic glial expression in these models. These findings were corroborated in post-mortem samples of patients with Alzheimer's disease, the most common tauopathy. Our results show that neurons with accumulated TAU induce the expression of the CB2 receptor, which enhances neurodegeneration. These results are important for our understanding of disease mechanisms, providing a novel therapeutic strategy to be investigated in tauopathies.

Keywords

ActivationAdultAgedAged, 80 and overAlzheimer diseaseAlzheimer's diseaseAlzheimers-diseaseAlzheimer’s diseaseAnandamideAnimalsBrainCannabinoid receptorCb2Endocannabinoid systemFemaleHumansHyperphosphorylationMaleMapt protein, humanMiceMice, inbred c57blMice, knockoutMice, transgenicMiddle agedMouse modelNeurodegenerationNeurodegenerative diseasesNeuroinflammatioNeuroinflammationNeuroprotectionPathologPhenotypeReceptor, cannabinoid, cb2RelevanceTauTau proteinsTauopathies

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Acta Neuropathologica Communications 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, 2021, it was in position 37/275, thus managing to position itself as a Q1 (Primer Cuartil), in the category Neurosciences.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.45. This 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: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Field Citation Ratio (FCR) from Dimensions: 4.94 (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-02, the following number of citations:

  • WoS: 21
  • Europe PMC: 19

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 2025-08-02:

  • 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: 54.
  • 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: 61 (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: 20.2.
  • The number of mentions on the social network X (formerly Twitter): 15 (Altmetric).
  • The number of mentions in news outlets: 1 (Altmetric).

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.

Leadership analysis of institutional authors

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) .