Academic Journal
Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration
| العنوان: | Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration |
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| المؤلفون: | Galán-Ganga, Marcos, Rodríguez-Cueto, Carmen, Merchán-Rubira, Jesús, Hernández, Félix, Ávila, Jesús, Lanciego, José Luis, Luengo, Elisa, López, M. G., Rábano, Alberto, Fernández-Ruiz, Jorge, Lastres-Becker, Isabel |
| المساهمون: | Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Fundación Tatiana Pérez de Guzmán el Bueno |
| سنة النشر: | 2021 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| الوصف: | 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 CB 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, CB ablation in mice protects from neurodegeneration induced by hTAU overexpression, corroborated at the level of cognitive behaviour, synaptic plasticity, and aggregates of insoluble TAU. At the level of neuroinflammation, the absence of CB 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 CB receptor, which enhances neurodegeneration. These results are important for our understanding of disease mechanisms, providing a novel therapeutic strategy to be investigated in tauopathies. ; 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 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 2051-5960 |
| Relation: | Publisher's version; http://dx.doi.org/10.1186/s40478-021-01196-5; Sí; Acta neuropathologica communications 9 (2021); http://hdl.handle.net/10261/256039; http://dx.doi.org/10.13039/100012818; http://dx.doi.org/10.13039/501100010805; http://dx.doi.org/10.13039/501100003329 |
| DOI: | 10.1186/s40478-021-01196-5 |
| DOI: | 10.13039/100012818 |
| DOI: | 10.13039/501100010805 |
| DOI: | 10.13039/501100003329 |
| الاتاحة: | http://hdl.handle.net/10261/256039 https://doi.org/10.1186/s40478-021-01196-5 https://doi.org/10.13039/100012818 https://doi.org/10.13039/501100010805 https://doi.org/10.13039/501100003329 |
| Rights: | open |
| رقم الانضمام: | edsbas.21CA261E |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20515960 |
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| DOI: | 10.1186/s40478-021-01196-5 |