Research Topic

Targeting the Endocannabinoidome in Neurodegenerative Disorders

About this Research Topic

Humans have been using Cannabis sativa /marijuana for millennia. However, only in the late 20th century, synthetic cannabinoids found in marijuana, like dronabinol (marinol) and nabilone have been approved by the FDA for use in cancer and HIV-AIDS and more recently canabidiol (epidiolex) for Dravet and Lennox Gastaut syndrome.

The first cannabis-derived compound (Nabiximols), sativex was approved for multiple sclerosis-related spasticity. This drug contains a standardized extract of tetrahydrocannabinol (THC), and the non-euphorigenic cannabinoid cannabidiol (CBD) in a 1:1 formulation. On the dark side, THC and its synthetic analogue nabilone were ineffective in clinical trials against the primary symptoms of Alzheimer´s disease (AD), Parkinson´s disease (PD) and Multiple Sclerosis (MS).

THC and nabilone are cannabinoid receptor 1 (CB1R) and receptor 2 (CB2R) partial agonists, similarly to the endocannabinoid N‐arachidonoyl‐ethanolamine (AEA), whereas the endocannabinoid 2‐arachidonoylglycerol (2‐AG) is a full CB1 and CB2 receptor agonist. Interestingly, CBD is a negative allosteric modulator of CB1R and interacts with other targets including Transient Receptor Potential (TRP) superfamily of cation channels, endocannabinoid (eCB) transporters and fatty acid amide hydrolase 1(FAAH) and equilibrative nucleoside transporter (ENT).

Nonetheless, the endocannabinoid system is altered in neurodegenerative disorders including AD, PD and MS. Moreover, eCBs can activate different receptors like transient receptor potential vanilloid 1 (TRPV1) channel and Peroxisome proliferator-activated receptor-γ (PPARγ). Their biosynthetic and catabolic signalling pathways are often shared with endocannabinoid congener mediators (eg. N-acylethanolamines) and other long-chain fatty acid amide-derived mediators (eg. N-acyl-neurotransmitters). Consequently, this complex network is often designated as endocannabinoidome.

Neurodegenerative diseases are debilitating, and the existing treatments are very limited and are only symptomatic. Therefore, the current Research Topic focuses on targeting endocannabinoidome as a promising disease-modifying strategy in neurodegenerative disorders. We are specifically seeking preclinical and clinical articles focused on the following areas in relation with neurorepair:

1. Endocannabinoid and endocannabinoid-like mediators;
2. Endocannabinoid anabolic enzymes;
3. Endocannabinoid catabolic enzymes;
4. CB1 and CB2 receptors and other endocannabinoidome receptors ;
5. Phytocannabinoid;
6. Synthetic cannabinoids.


Keywords: cannabinoids, endocannabinoid system, endocannabinoidome, neurodegenerative disorders, neurorepair


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Humans have been using Cannabis sativa /marijuana for millennia. However, only in the late 20th century, synthetic cannabinoids found in marijuana, like dronabinol (marinol) and nabilone have been approved by the FDA for use in cancer and HIV-AIDS and more recently canabidiol (epidiolex) for Dravet and Lennox Gastaut syndrome.

The first cannabis-derived compound (Nabiximols), sativex was approved for multiple sclerosis-related spasticity. This drug contains a standardized extract of tetrahydrocannabinol (THC), and the non-euphorigenic cannabinoid cannabidiol (CBD) in a 1:1 formulation. On the dark side, THC and its synthetic analogue nabilone were ineffective in clinical trials against the primary symptoms of Alzheimer´s disease (AD), Parkinson´s disease (PD) and Multiple Sclerosis (MS).

THC and nabilone are cannabinoid receptor 1 (CB1R) and receptor 2 (CB2R) partial agonists, similarly to the endocannabinoid N‐arachidonoyl‐ethanolamine (AEA), whereas the endocannabinoid 2‐arachidonoylglycerol (2‐AG) is a full CB1 and CB2 receptor agonist. Interestingly, CBD is a negative allosteric modulator of CB1R and interacts with other targets including Transient Receptor Potential (TRP) superfamily of cation channels, endocannabinoid (eCB) transporters and fatty acid amide hydrolase 1(FAAH) and equilibrative nucleoside transporter (ENT).

Nonetheless, the endocannabinoid system is altered in neurodegenerative disorders including AD, PD and MS. Moreover, eCBs can activate different receptors like transient receptor potential vanilloid 1 (TRPV1) channel and Peroxisome proliferator-activated receptor-γ (PPARγ). Their biosynthetic and catabolic signalling pathways are often shared with endocannabinoid congener mediators (eg. N-acylethanolamines) and other long-chain fatty acid amide-derived mediators (eg. N-acyl-neurotransmitters). Consequently, this complex network is often designated as endocannabinoidome.

Neurodegenerative diseases are debilitating, and the existing treatments are very limited and are only symptomatic. Therefore, the current Research Topic focuses on targeting endocannabinoidome as a promising disease-modifying strategy in neurodegenerative disorders. We are specifically seeking preclinical and clinical articles focused on the following areas in relation with neurorepair:

1. Endocannabinoid and endocannabinoid-like mediators;
2. Endocannabinoid anabolic enzymes;
3. Endocannabinoid catabolic enzymes;
4. CB1 and CB2 receptors and other endocannabinoidome receptors ;
5. Phytocannabinoid;
6. Synthetic cannabinoids.


Keywords: cannabinoids, endocannabinoid system, endocannabinoidome, neurodegenerative disorders, neurorepair


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

04 August 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

04 August 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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