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

Galán-Ganga, Marcos; Rı́o, Rocı́o del; Jiménez-Moreno, Natalia; Dı́az-Guerra, Margarita; Lastres‐Becker, Isabel

doi:10.1007/s10571-019-00719-y

Cited by 28 publications

(23 citation statements)

References 51 publications

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“…69 Therefore, it is not surprising that CB2 agonists can effectively alleviate oxidative stress and inflammatory responses by activating the Nrf2 pathway. 70,71 Combining these results and previous reports, we anticipate that CB2 agonists may be beneficial for treating GC-induced ONFH.…”

Section: Discussionsupporting

confidence: 76%

Inhibition of MAGL activates the Keap1/Nrf2 pathway to attenuate glucocorticoid‐induced osteonecrosis of the femoral head

Yang

Sun

Xue

et al. 2021

Clinical & Translational Med

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Section: Discussionsupporting

confidence: 76%

Inhibition of MAGL activates the Keap1/Nrf2 pathway to attenuate glucocorticoid‐induced osteonecrosis of the femoral head

Yang

Sun

Xue

et al. 2021

Clinical & Translational Med

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“…These studies indicated targeting the CB2 receptor might represent a viable way for neuroinflammation modification in PD. CB2 receptor activation has been reported to inhibit neurotoxin-mediated neuroinflammation through regulating multiple molecules, including NRF2, ERK1/2, cPLA2, and NF-κB ( Ribeiro et al, 2013 ; Galán-Ganga et al, 2020 ). Importantly, a much more intense deterioration of tyrosine hydroxylase (TH)-containing nigral neurons in CB2 receptor-deficient mice compared to wild-type animals ( Gómez-Gálvez et al, 2016 ), indicating a potential neuroprotective role for CB2 receptor.…”

Section: Role Of Cannabinoid Receptors In Microglial Activation Of Parkinson’s Diseasementioning

confidence: 99%

Role of G Protein-Coupled Receptors in Microglial Activation: Implication in Parkinson’s Disease

Chen

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is one of the prevalent neurodegenerative diseases associated with preferential loss of dopaminergic (DA) neurons in the substantia nigra compacta (SNc) and accumulation of α-synuclein in DA neurons. Even though the precise pathogenesis of PD is not clear, a large number of studies have shown that microglia-mediated neuroinflammation plays a vital role in the process of PD development. G protein-coupled receptors (GPCRs) are widely expressed in microglia and several of them act as regulators of microglial activation upon corresponding ligands stimulations. Upon α-synuclein insults, microglia would become excessively activated through some innate immune receptors. Presently, as lack of ideal drugs for treating PD, certain GPCR which is highly expressed in microglia of PD brain and mediates neuroinflammation effectively could be a prospective source for PD therapeutic intervention. Here, six kinds of GPCRs and two types of innate immune receptors were introduced, containing adenosine receptors, purinergic receptors, metabotropic glutamate receptors, adrenergic receptors, cannabinoid receptors, and melatonin receptors and their roles in neuroinflammation; we highlighted the relationship between these six GPCRs and microglial activation in PD. Based on the existing findings, we tried to expound the implication of microglial GPCRs-regulated neuroinflammation to the pathophysiology of PD and their potential to become a new expectation for clinical therapeutics.

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“…CB 2 cannabinoid receptors have been traditionally found in higher levels in cells from the immune system and microglia [30], where they participate in the modulation of inflammation [16,48]. However, recent publications have pointed their expression in neurons of the central nervous system, despite the problems of specificity shown by the different antibodies developed so far (review [8]).…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration

Galán-Ganga

Rodríguez‐Cueto

Merchán-Rubira

et al. 2021

acta neuropathol commun

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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.

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

Abstract: y. Please refer to any applicable terms of use of the publisher.

Cited by 28 publications

References 51 publications

Inhibition of MAGL activates the Keap1/Nrf2 pathway to attenuate glucocorticoid‐induced osteonecrosis of the femoral head

Inhibition of MAGL activates the Keap1/Nrf2 pathway to attenuate glucocorticoid‐induced osteonecrosis of the femoral head

Role of G Protein-Coupled Receptors in Microglial Activation: Implication in Parkinson’s Disease

Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration

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