Potential Role of Cannabinoid Type 2 Receptors in Neuropsychiatric and Neurodegenerative Disorders

Ishiguro, Hiroki; Kibret, Berhanu Geresu; Horiuchi, Yasue; Onaivi, Emmanuel S.

doi:10.3389/fpsyt.2022.828895

Cited by 17 publications

(14 citation statements)

References 220 publications

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“…It is worth mentioning that CB2 receptors are highly inducible [ 38 ]. In physiological conditions, the brain CB2 receptors are expressed at low levels, whereas in pathological conditions, including neurodegenerative diseases, their expression is enhanced and up-regulated [ 39 ].…”

Section: The Cannabinoid Type 2 (Cb2) Receptors In Pdmentioning

confidence: 99%

The Role of Cannabinoid Type 2 Receptors in Parkinson’s Disease

Basile

Mazzon

2022

Biomedicines

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Parkinson’s disease (PD) is the second most frequent neurodegenerative disease and currently represents a clear unmet medical need. Therefore, novel preventive and therapeutic strategies are needed. Cannabinoid type 2 (CB2) receptors, one of the components of the endocannabinoid system, can regulate neuroinflammation in PD. Here, we review the current preclinical and clinical studies investigating the CB2 receptors in PD with the aim to clarify if these receptors could have a role in PD. Preclinical data show that CB2 receptors could have a neuroprotective action in PD and that the therapeutic targeting of CB2 receptors could be promising. Indeed, it has been shown that different CB2 receptor-selective agonists exert protective effects in different PD models. Moreover, the alterations in the expression of CB2 receptors observed in brain tissues from PD animal models and PD patients suggest the potential value of CB2 receptors as possible novel biomarkers for PD. However, to date, there is no direct evidence of the role of CB2 receptors in PD. Further studies are strongly needed in order to fully clarify the role of CB2 receptors in PD and thus pave the way to novel possible diagnostic and therapeutic opportunities for PD.

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Section: The Cannabinoid Type 2 (Cb2) Receptors In Pdmentioning

confidence: 99%

The Role of Cannabinoid Type 2 Receptors in Parkinson’s Disease

Basile

Mazzon

2022

Biomedicines

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“…However, there is evidence of neuronal expression in the postsynaptic neurons, where its activation could hyperpolarize cells and inhibit signal transmission [171,172]. Their expression is much lower than that of CB1 and it can be increased by several stimuli [170,173].…”

Section: The Ecb System In Neuroimmune and Behavioral Response To Str...mentioning

confidence: 99%

“…Repeated homotypic stress potentiates these effects on eCB levels, and reduces the expression of CB1 in most brain areas, such as hippocampus and amygdala, whereas increases it in the PFC [174]. Impaired CB1 signaling by AEA result in a lack of adaptation to repeated stress and consequently, behavioral changes [175], and impaired CB2 signaling could contribute to neuroinflammation [173]. Data regarding heterotypic stressors on eCB levels are less consistent [176].…”

Section: The Ecb System In Neuroimmune and Behavioral Response To Str...mentioning

confidence: 99%

Toll-like receptor 4 in the interface between neuroimmune response and behavioral alterations caused by stress

Souza-Junior

Cunha

Lisboa

2022

Explor Neuroprot Ther

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Different stressors can elicit neuroinflammatory responses modulated by innate immunity receptors, such as the family of Toll-like receptors (TLRs). The TLR4, a pattern recognition receptor (PRR), is involved in many diseases, such as inflammatory and central nervous system (CNS) diseases. Stress exposure can regulate the expression of PRRs, including TLR4, in the brain of animals, especially in the hippocampus and prefrontal cortex. Moreover, TLR4 modulates behavior and neuroinflammatory responses in the brain. In addition, to TLR4, the endocannabinoid (eCB) system plays a role in stress response and immunity, acting as a regulatory, stress-buffer system. This system is involved in many TLRs-mediated immune responses, such as microglia activation. Therefore, pharmacological approaches targeting the eCB system could modulate neuroinflammatory responses to stress by interfering with the TLR4 pathway. Although the connection between TLR4, stress, and neuroinflammation is well documented, almost no pre-clinical studies investigate the possible direct relationship between TLR4, behavior, stress, and the eCB system. Studies exploring the relationship between stress, neuroinflammation, TLR4, and the eCB system were searched using Pubmed, Web of Science, and Embase databases. Based on this search, this review is focused on the involvement of TLR4 receptors and signaling in neuroinflammation and the behavioral consequences of stress exposure. Moreover, evidence of the eCB system modulating TLR4-mediated responses was brought to the attention, pointing out a possible regulatory role of these responses by eCBs in behavior changes related to mood disorders.

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“…Cannabinoid 2 receptors (CB2Rs), one type of cannabinoid receptor, are found in peripheral tissues of immunological origin ( Munro et al, 1993 ; Brown et al, 2002 ) and are distributed in different brain regions ( Ishiguro et al, 2022 ). CB2Rs are post-synaptically expressed and up-regulated in response to injury and inflammation ( Ishiguro et al, 2022 ). CB2Rs are mainly distributed in OC, spiral ligament and SGN cells in the cochlea of rats and mice ( Kim et al, 2014 ; Kaur et al, 2016 ; Ghosh et al, 2018 ).…”

Section: Roles Of Class a G Protein-coupled Receptors In Cochleamentioning

confidence: 99%

G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss

Guo²,

Fu³

et al. 2022

Front. Mol. Neurosci.

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The prevalence of hearing loss-related diseases caused by different factors is increasing worldwide year by year. Currently, however, the patient’s hearing loss has not been effectively improved. Therefore, there is an urgent need to adopt new treatment measures and treatment techniques to help improve the therapeutic effect of hearing loss. G protein-coupled receptors (GPCRs), as crucial cell surface receptors, can widely participate in different physiological and pathological processes, particularly play an essential role in many disease occurrences and be served as promising therapeutic targets. However, no specific drugs on the market have been found to target the GPCRs of the cochlea. Interestingly, many recent studies have demonstrated that GPCRs can participate in various pathogenic process related to hearing loss in the cochlea including heredity, noise, ototoxic drugs, cochlear structure, and so on. In this review, we comprehensively summarize the functions of 53 GPCRs known in the cochlea and their relationships with hearing loss, and highlight the recent advances of new techniques used in cochlear study including cryo-EM, AI, GPCR drug screening, gene therapy vectors, and CRISPR editing technology, as well as discuss in depth the future direction of novel GPCR-based drug development and gene therapy for cochlear hearing loss. Collectively, this review is to facilitate basic and (pre-) clinical research in this area, and provide beneficial help for emerging GPCR-based cochlear therapies.

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Potential Role of Cannabinoid Type 2 Receptors in Neuropsychiatric and Neurodegenerative Disorders

Cited by 17 publications

References 220 publications

The Role of Cannabinoid Type 2 Receptors in Parkinson’s Disease

The Role of Cannabinoid Type 2 Receptors in Parkinson’s Disease

Toll-like receptor 4 in the interface between neuroimmune response and behavioral alterations caused by stress

G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss

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