GPR55: A therapeutic target for Parkinson's disease?

Celorrio, Marta; Rojo-Bustamante, Estefanía; Fernández-Suárez, Diana; Sáez, Elena; Mendoza, Ander Estella-Hermoso de; Müller, Christa E.; Ramı́rez, Marı́a J.; Oyarzábal, Julen; Franco, Rafael; Aymerich, Marta

doi:10.1016/j.neuropharm.2017.08.017

Cited by 78 publications

(89 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, we propose that the tetrad effects observed in WT mice could be the final balance between two opposite actions—CB 1 /CB 2 ‐mediated tetrad‐enhancing effects and GPR55‐mediated tetrad‐attenuating effects. This hypothesis is supported by the findings that GPR55 stimulation by abnormal‐cannabidiol (abn‐CBD) attenuated haloperidol‐induced catalepsy (Celorrio et al, ), while GPR55 deletion impaired locomotor performance (Bjursell et al, ; Celorrio et al, ; Meadows et al, ; Wu et al, ) and produced anti‐nociceptive (analgesic) effects in rat inflammatory and neuropathic pain models (Staton et al, ).…”

Section: Discussionmentioning

confidence: 90%

“…In addition, GPR55, another putative cannabinoid receptor (Baker, Pryce, Davies, & Hiley, ; Moriconi, Cerbara, Maccarrone, & Topai, ), was also found in brain regions involved in locomotion and nociception (Martínez‐Pinilla et al, ; Ryberg et al, ; Wu et al, ). It has been reported that GPR55 agonists inhibited haloperidol‐induced catalepsy (Celorrio et al, ), whereas a GPR55 antagonist reduced locomotor activity (Rahimi, Hajizadeh Moghaddam, & Roohbakhsh, ). Genetic deletion of GPR55 altered nociceptive responses in multiple pain models in rodents (Bjursell et al, ; Rahimi et al, ; Staton et al, ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Different receptor mechanisms underlying phytocannabinoid‐ versus synthetic cannabinoid‐induced tetrad effects: Opposite roles of CB₁/CB₂ versus GPR55 receptors

Xiaofei

Galaj

et al. 2020

British J Pharmacology

View full text Add to dashboard Cite

Background and Purpose Cannabis or cannabinoids produce characteristic tetrad effects—analgesia, hypothermia, catalepsy and suppressed locomotion, which are believed to be mediated by the activation of cannabinoid CB1 receptors. Given recent findings of CB2 and GPR55 receptors in the brain, we examined whether these receptors are also involved in cannabinoid action. Experimental Approach We compared Δ9‐tetrahydrocannabinol (Δ9‐THC)‐, WIN55212‐2‐, or XLR11‐induced tetrad effects between wild‐type (WT) and each genotype of CB1‐, CB2‐ or GPR55‐knockout (KO) mice and then observed the effects of antagonists of these receptors on these tetrad effects in WT mice. Key Results Systemic administration of Δ9‐THC, WIN55212‐2 or XLR11 produced dose‐dependent tetrad effects in WT mice. Genetic deletion or pharmacological blockade of CB1 receptors abolished the tetrad effects produced by all three cannabinoids. Unexpectedly, genetic deletion of CB2 receptor abolished analgesia and catalepsy produced by Δ9‐THC or WIN55212‐2, but not by XLR11. Microinjections of Δ9‐THC into the lateral ventricles also produced tetrad effects in WT, but not in CB1‐KO mice. CB2‐KO mice displayed a reduction in intraventricular Δ9‐THC‐induced analgesia and catalepsy. In contrast to CB1 and CB2 receptors, genetic deletion of GPR55 receptors caused enhanced responses to Δ9‐THC or WIN55212‐2. Antagonisim of CB1, CB2 or GPR55 receptors produced alterations similar to those observed in each genotype mouse line. Conclusions and Implications These findings suggest that in addition to CB1, both CB2 and GPR55 receptors are also involved in some pharmacological effects produced by cannabinoids. CB1/CB2, in contrast to GPR55, receptors appears to play opposite roles in cannabinoid action.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Different receptor mechanisms underlying phytocannabinoid‐ versus synthetic cannabinoid‐induced tetrad effects: Opposite roles of CB₁/CB₂ versus GPR55 receptors

Xiaofei

Galaj

et al. 2020

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…This chronic mouse model of PD was treated with abnormal-CBD (Abn-CBD), a synthetic CBD isomer and GPR55 agonist. Authors found that the key features of PD induced by MPTPp were prevented by the pharmacological treatment, suggesting that the activation of GPR55 may be a good strategy for the treatment of PD (Celorrio et al, 2017).…”

Section: Cbd and Pdmentioning

confidence: 99%

From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases

et al. 2020

View full text Add to dashboard Cite

Cannabis sativa, commonly known as marijuana, contains a pool of secondary plant metabolites with therapeutic effects. Besides D9-tetrahydrocannabinol that is the principal psychoactive constituent of Cannabis, cannabidiol (CBD) is the most abundant nonpsychoactive phytocannabinoid and may represent a prototype for antiinflammatory drug development for human pathologies where both the inflammation and oxidative stress (OS) play an important role to their etiology and progression. To this regard, Alzheimer's disease (AD), Parkinson's disease (PD), the most common neurodegenerative disorders, are characterized by extensive oxidative damage to different biological substrates that can cause cell death by different pathways. Most cases of neurodegenerative diseases have a complex etiology with a variety of factors contributing to the progression of the neurodegenerative processes; therefore, promising treatment strategies should simultaneously target multiple substrates in order to stop and/ or slow down the neurodegeneration. In this context, CBD, which interacts with the eCB system, but has also cannabinoid receptor-independent mechanism, might be a good candidate as a prototype for anti-oxidant drug development for the major neurodegenerative disorders, such as PD and AD. This review summarizes the multiple molecular pathways that underlie the positive effects of CBD, which may have a considerable impact on the progression of the major neurodegenerative disorders.

show abstract

“…and these mechanisms have been described for AD in the previous subsection (see 2.2.4.). However, a lack of neuroprotective activity was described for CBD in the chronic MPTP mouse model [164]. The phytocannabinoid ∆ 9 -THCV, with its antioxidant properties and the ability to activate CB 2 and to block CB 1 receptors, presents an interesting pharmacological profile for PD.…”

Section: The Endocannabinoid System In Parkinson's Diseasementioning

confidence: 99%

Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system

Aymerich

Aso

Abellanas

et al. 2018

Biochemical Pharmacology

View full text Add to dashboard Cite

The endocannabinoid system (ECS) exerts a modulatory effect of important functions such as neurotransmission, glial activation, oxidative stress, or protein homeostasis. Dysregulation of these cellular processes is a common neuropathological hallmark in aging and in neurodegenerative diseases of the central nervous system (CNS). The broad spectrum of actions of cannabinoids allows targeting different aspects of these multifactorial diseases. In this review, we examine the therapeutic potential of the ECS for the treatment of chronic neurodegenerative diseases of the CNS focusing on Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. First, we describe the localization of the molecular components of the ECS and how they are altered under neurodegenerative conditions, either contributing to or protecting cells from degeneration. Second, we address recent advances in the modulation of the ECS using experimental models through different strategies including the direct targeting of cannabinoid receptors with agonists or antagonists, increasing the endocannabinoid tone by the inhibition of endocannabinoid hydrolysis, and activation of cannabinoid receptor-independent effects. Preclinical evidence indicates that cannabinoid pharmacology is complex but supports the therapeutic potential of targeting the ECS. Third, we review the clinical evidence and discuss the future perspectives on how to bridge human and animal studies to develop cannabinoid-based therapies for each neurodegenerative disorder. Finally, we summarize the most relevant opportunities of cannabinoid pharmacology related to each disease and the multiple unexplored pathways in cannabinoid pharmacology that could be useful for the treatment of neurodegenerative diseases.

show abstract

GPR55: A therapeutic target for Parkinson's disease?

Cited by 78 publications

References 50 publications

Different receptor mechanisms underlying phytocannabinoid‐ versus synthetic cannabinoid‐induced tetrad effects: Opposite roles of CB₁/CB₂ versus GPR55 receptors

Different receptor mechanisms underlying phytocannabinoid‐ versus synthetic cannabinoid‐induced tetrad effects: Opposite roles of CB₁/CB₂ versus GPR55 receptors

From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases

Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system

Contact Info

Product

Resources

About

GPR55: A therapeutic target for Parkinson's disease?

Cited by 78 publications

References 50 publications

Different receptor mechanisms underlying phytocannabinoid‐ versus synthetic cannabinoid‐induced tetrad effects: Opposite roles of CB1/CB2 versus GPR55 receptors

Different receptor mechanisms underlying phytocannabinoid‐ versus synthetic cannabinoid‐induced tetrad effects: Opposite roles of CB1/CB2 versus GPR55 receptors

From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases

Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system

Contact Info

Product

Resources

About

Different receptor mechanisms underlying phytocannabinoid‐ versus synthetic cannabinoid‐induced tetrad effects: Opposite roles of CB₁/CB₂ versus GPR55 receptors

Different receptor mechanisms underlying phytocannabinoid‐ versus synthetic cannabinoid‐induced tetrad effects: Opposite roles of CB₁/CB₂ versus GPR55 receptors