Effect of endocannabinoid signalling on cell fate: life, death, differentiation and proliferation of brain cells

Garcı́a-Arencibia, Moisés; Molina‐Holgado, Eduardo; Molina-Holgado, Francisco

doi:10.1111/bph.14369

Cited by 32 publications

(30 citation statements)

References 95 publications

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“…ECS takes part in the regulation of neurogenesis and neurodegeneration [161]. Most studies suggest that endocannabinoid signaling is usually beneficial in this context.…”

Section: Neurodegenerationmentioning

confidence: 99%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands’ synthesizing and degrading enzymes, are promising therapeutic targets. Their modulation has been employed in or extensively studied as a treatment of multiple diseases. However, due to a complex nature of ECS and its crosstalk with other biological systems, the development of novel drugs turned out to be a challenging task. In this review, we summarize potential therapeutic applications for ECS-targeting drugs, especially focusing on promising synthetic compounds and preclinical studies. We put emphasis on modulation of specific proteins of ECS in different pathophysiological areas. In addition, we stress possible difficulties and risks and highlight proposed solutions. By presenting this review, we point out information pivotal in the spotlight of ECS-targeting drug design, as well as provide an overview of the current state of knowledge on ECS-related pharmacodynamics and show possible directions for needed research.

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“…ECS takes part in the regulation of neurogenesis and neurodegeneration [161]. Most studies suggest that endocannabinoid signaling is usually beneficial in this context.…”

Section: Neurodegenerationmentioning

confidence: 99%

A Guide to Targeting the Endocannabinoid System in Drug Design

Stasiulewicz

Znajdek

Grudzień

et al. 2020

IJMS

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“…129,130 Altogether, the ECS regulates cellular plasticity in the adult brain. Here, we focused on proliferation, but the ECS can also regulate various aspects of apoptosis and autophagy, 131 two important cellular events for maintaining homeostasis in the body.…”

Section: Generation Of New Oligodendrocytesmentioning

confidence: 99%

Cannabinoids

2020

Dialogues Clin Neurosci

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Dialogues in Clinical Neuroscience is a quarterly publication that aims to serve as an interface between clinical neuropsychiatry and the neurosciences by providing state-of-the-art information and original insights into relevant clinical, biological, and therapeutic aspects. Each issue addresses a specific topic, and also publishes free contributions in the field of neuroscience as well as other non-topic-related material. All contributions are reviewed by members of the Editorial Board and submitted to expert consultants for peer review.

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“…Cannabinoids are a family of pleiotropic compounds identified for the first time in the cannabis plant (phytocannabinoids) but which can also be obtained in the laboratory (synthetic cannabinoids) and are present in animal tissues (endocannabinoids). In general, they are active at the so-called endocannabinoid system, a modulatory system involved in the maintenance of cell and tissue homeostasis (reviewed recently in García-Arencibia et al, 2018). Given the importance of this homeostatic role in the cell integrity, the endocannabinoid system has been strongly associated with the survival/death cell decision, so that those cannabinoids capable of targeting and activating/inhibiting specific endocannabinoid elements are able to exert both cytoprotective/cytorepair properties (reviewed recently in Fernández-Ruiz, 2018) and proapoptotic/antitumoral effects (reviewed in Velasco et al, 2016).…”

Section: Brief Overview On Cannabinoids As Neuroprotectantsmentioning

confidence: 99%

Endocannabinoid System in Spinocerebellar Ataxia Type-3 and Other Autosomal-Dominant Cerebellar Ataxias: Potential Role in Pathogenesis and Expected Relevance as Neuroprotective Targets

Gómez‐Ruiz

Rodríguez‐Cueto

Luna-Piñel

et al. 2019

Front. Mol. Neurosci.

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Spinocerebellar ataxias (SCAs) are a group of hereditary and progressive neurological disorders characterized by a loss of balance and motor coordination typically associated with cerebellar atrophy. The most prevalent SCA types are all polyQ disorders like Huntington’s disease, sharing the most relevant events in pathogenesis with this basal ganglia disorder, but with most of the damage concentrated in cerebellar neurons, and in their afferent and efferent connections (e.g., brainstem nuclei). SCAs have no cure and effective symptom-alleviating and disease-modifying therapies are not currently available. However, based on results obtained in studies conducted in murine models and information derived from analyses in post-mortem tissue samples from patients, which show notably higher levels of CB 1 receptors found in different cerebellar neuronal subpopulations, the blockade of these receptors has been proposed for acutely modulating motor incoordination in cerebellar ataxias, whereas their chronic activation has been proposed for preserving specific neuronal losses. Additional studies in post-mortem tissues from SCA patients have also demonstrated elevated levels of CB 2 receptors in Purkinje neurons as well as in glial elements in the granular layer and in the cerebellar white matter, with a similar profile found for endocannabinoid hydrolyzing enzymes, then suggesting that activating CB 2 receptors and/or inhibiting these enzymes may also serve to develop cannabinoid-based neuroprotective therapies. The present review will address both aspects. On one hand, the endocannabinoid system becomes dysregulated in the cerebellum and also in other CNS structures (e.g., brainstem, basal ganglia) in SCAs, which may contribute to the progression of pathogenic events in these diseases. On the other hand, these endocannabinoid alterations may be pharmacologically corrected or enhanced, and this may have therapeutic consequences, either alleviating specific symptoms or eliciting neuroprotective effects, an objective presently under investigation.

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Effect of endocannabinoid signalling on cell fate: life, death, differentiation and proliferation of brain cells

Cited by 32 publications

References 95 publications

A Guide to Targeting the Endocannabinoid System in Drug Design

A Guide to Targeting the Endocannabinoid System in Drug Design

Cannabinoids

Endocannabinoid System in Spinocerebellar Ataxia Type-3 and Other Autosomal-Dominant Cerebellar Ataxias: Potential Role in Pathogenesis and Expected Relevance as Neuroprotective Targets

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