An overview of the cannabinoid type 2 receptor system and its therapeutic potential

Bie, Bihua; Wu, Jiang; Foss, Joseph F.; Naguib, Mohamed

doi:10.1097/aco.0000000000000616

Cited by 138 publications

(101 citation statements)

References 108 publications

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“…22) Accordingly, NITyr could obviously decrease the release of inflammatory cytokines that could induce the inflammatory cascade, thereby ameliorate central nervous systems disorders. 23) Meanwhile, lipid peroxidation products and the activities of antioxidant enzymes were strikingly ameliorated in the NITyr group consisted with our previous observations of N-stearoyl amino acids in ischemiareperfusion injury. 6) NITyr could reduce the level of MDA and enhance the activities of SOD and CAT but not GPx.…”

Section: Discussionsupporting

confidence: 73%

N-Linoleyltyrosine Protects against Transient Cerebral Ischemia in Gerbil via CB2 Receptor Involvement in PI3K/Akt Signaling Pathway

Cheng

Zhou

et al. 2019

Biological & Pharmaceutical Bulletin

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Anandamide (AEA) played potent neuroprotective activities via cannabinoid type 1 (CB1) and 2 (CB2) receptor. N-Linoleyltyrosine (NITyr), as an AEA analogue, was synthesized in our laboratory and evaluated the neuroprotective effects and mechanisms for the first time. NITyr was synthesized via substitution reaction. The neuroprotective effects of NITyr were evaluated in a gerbil model of transient cerebral ischemia. Each gerbil was subjected to open field test (OFT), Rotard rod test (RRT), Morris water maze (MWM)successively and executed after animal behaviors. Part of the brain was stained with hematoxylin and eosin (HE) and Nissl staining, and the rest for biochemical analysis. NITyr could not increase spontaneous locomotor activity and ameliorate the anxiety behavior in the OFT but could improve the motor coordination in the RRT and the spatial memory impairment in the MWM. Immunohistochemically, NITyr could attenuate the ischemia-induced neural loss in the hippocampus. The Enzyme-linked immunosorbent assay (ELISA) suggested that NITyr ameliorated the inflammation and oxidative stress. Consistently, NITyr could up-regulate the expressions of p-phosphadylinositol 3-kinase (PI3K) and p-Akt but not PI3K and Akt in the hippocampus. In addition to oxidative stress, CB2 receptor antagonist AM630 but not CB1 receptor antagonist AM251 could reverse the above phenomena. However, CB1 receptor antagonist AM251 could reverse oxidative stress. Accordingly, NITyr could up-regulate the expressions of CB2 but not CB1. NITyr could improve the motor coordination, learning and memory impairments, neural loss in the hippocampus and the inflammation of the mice via CB2 receptor involvement of PI3K/Akt signaling pathway.

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Section: Discussionsupporting

confidence: 73%

N-Linoleyltyrosine Protects against Transient Cerebral Ischemia in Gerbil via CB2 Receptor Involvement in PI3K/Akt Signaling Pathway

Cheng

Zhou

et al. 2019

Biological & Pharmaceutical Bulletin

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“…CB2 receptors are also present in glial cells (e.g., microglia), which were observed to be upregulated following inflammation or nerve injury [109][110][111][112]. Microglia are important mediators for neuropathic pain development [113][114][115].…”

Section: Modulation Of Cb2 Receptor Expression Under Neuropathic Painmentioning

confidence: 99%

“…CB2 receptors expressed in keratinocytes were increased under inflammatory or infectious conditions [118,119]. The presence of CB2 receptors in glial and inflammatory cells makes them attractive targets to reduce pain under inflammatory and neuropathic pain conditions [111,120].…”

Section: Modulation Of Cb2 Receptor Expression Under Neuropathic Painmentioning

confidence: 99%

Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

Hossain

Ando

Unno

2020

IJMS

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Neuropathic pain conditions including neuropathic orofacial pain (NOP) are difficult to treat. Contemporary therapeutic agents for neuropathic pain are often ineffective in relieving pain and are associated with various adverse effects. Finding new options for treating neuropathic pain is a major priority in pain-related research. Cannabinoid-based therapeutic strategies have emerged as promising new options. Cannabinoids mainly act on cannabinoid 1 (CB1) and 2 (CB2) receptors, and the former is widely distributed in the brain. The therapeutic significance of cannabinoids is masked by their adverse effects including sedation, motor impairment, addiction and cognitive impairment, which are thought to be mediated by CB1 receptors in the brain. Alternative approaches have been developed to overcome this problem by selectively targeting CB2 receptors, peripherally restricted CB1 receptors and endocannabinoids that may be locally synthesized on demand at sites where their actions are pertinent. Many preclinical studies have reported that these strategies are effective for treating neuropathic pain and produce no or minimal side effects. Recently, we observed that inhibition of degradation of a major endocannabinoid, 2-arachydonoylglycerol, can attenuate NOP following trigeminal nerve injury in mice. This review will discuss the above-mentioned alternative approaches that show potential for treating neuropathic pain including NOP.

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“…In addition to an upregulation in AD, a substantial increase in CB 2 receptor expression has been found in human CNS tissue in a number of disorders associated with neuroinflammation, including MS, Down syndrome, and amyotrophic lateral sclerosis (ALS) [224,297,298]. It has been suggested that the upregulation and activation of the CB 2 receptor in neurodegenerative disease may be part of a type of negative-feedback loop in response to physiological stress, with the aim of limiting the inflammatory process (reviewed in [299]).…”

Section: The Cannabinoid System In Neuroinflammation and Neurodegenermentioning

confidence: 99%

Microglial Phenotypes and Their Relationship to the Cannabinoid System: Therapeutic Implications for Parkinson’s Disease

et al. 2020

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Parkinson’s disease is a neurodegenerative disorder, the motor symptoms of which are associated classically with Lewy body formation and nigrostriatal degeneration. Neuroinflammation has been implicated in the progression of this disease, by which microglia become chronically activated in response to α-synuclein pathology and dying neurons, thereby acquiring dishomeostatic phenotypes that are cytotoxic and can cause further neuronal death. Microglia have a functional endocannabinoid signaling system, expressing the cannabinoid receptors in addition to being capable of synthesizing and degrading endocannabinoids. Alterations in the cannabinoid system—particularly an upregulation in the immunomodulatory CB2 receptor—have been demonstrated to be related to the microglial activation state and hence the microglial phenotype. This paper will review studies that examine the relationship between the cannabinoid system and microglial activation, and how this association could be manipulated for therapeutic benefit in Parkinson’s disease.

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An overview of the cannabinoid type 2 receptor system and its therapeutic potential

Abstract: The functional involvement of CB2 receptor in neuropathic pain and other neuroinflammatory diseases highlights the potential therapeutic role of drugs acting at the CB2 receptor.

Cited by 138 publications

References 108 publications

<i>N</i>-Linoleyltyrosine Protects against Transient Cerebral Ischemia in Gerbil <i>via</i> CB2 Receptor Involvement in PI3K/Akt Signaling Pathway

<i>N</i>-Linoleyltyrosine Protects against Transient Cerebral Ischemia in Gerbil <i>via</i> CB2 Receptor Involvement in PI3K/Akt Signaling Pathway

Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

Microglial Phenotypes and Their Relationship to the Cannabinoid System: Therapeutic Implications for Parkinson’s Disease

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