2026-08-19T03:37:59Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/1134262025-03-18T14:14:32Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Galán Ganga, Marcos author Merchán Rubira, Jesús author Rodríguez Cueto, Carmen Aurora author Hernández F 2025-01-09T09:52:38Z 2025-01-09T09:52:38Z 2021-05-17 Galán-Ganga M, Rodríguez-Cueto C, Merchán-Rubira J, Hernández F, Ávila J, Posada-Ayala M, Lanciego JL, Luengo E, Lopez MG, Rábano A, Fernández-Ruiz J, Lastres-Becker I. Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration. Acta Neuropathol Commun. 2021 May 17;9(1):90. doi: 10.1186/s40478-021-01196-5. PMID: 34001284; PMCID: PMC8130522. 10.1186/s40478-021-01196-5 https://hdl.handle.net/20.500.14352/113426 https://doi.org/10.1186/s40478-021-01196-5 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 hTAUP301L 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. eng Attribution-NonCommercial-NoDerivatives 4.0 International Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration. journal article 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