Cannabidiol and the Canonical WNT/β-Catenin Pathway in Glaucoma

Abstract

Glaucoma is a progressive neurodegenerative disease which constitutes the main frequent cause of irreversible blindness. Recent findings have shown that oxidative stress, inflammation and glutamatergic pathway play key roles in the causes of glaucoma. Recent studies have shown a down regulation of the WNT/β-catenin pathway in glaucoma, associated with overactivation of the GSK-3β signaling. WNT/β-catenin pathway is mainly associated with oxidative stress, inflammation and glutamatergic pathway. Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa plant which possesses many therapeutic properties across a range of neuropsychiatric disorders. Since few years, CBD presents an increased interest as a possible drug in anxiolytic disorders. CBD administration is associated with increase of the WNT/β-catenin pathway and decrease of the GSK-3β activity. CBD has a lower affinity for CB1 but can act through other signaling in glaucoma, including the WNT/β-catenin pathway. CBD downregulates GSK3-β activity, an inhibitor of WNT/β-catenin pathway. Moreover, CBD was reported to suppress pro-inflammatory signaling and neuroinflammation, oxidative stress and glutamatergic pathway. Thus, this review focuses on the potential effects of cannabidiol, as a potential therapeutic strategy, on glaucoma and some of the presumed mechanisms by which this phytocannabinoid provides its possible benefit properties through the WNT/β-catenin pathway.

Anti-Cancer Activity of Cannabis sativa Phytocannabinoids: Molecular Mechanisms and Potential in the Fight against Ovarian Cancer and Stem Cells

“…THC (via CB1 activation) and CBD were shown to inhibit Akt phosphorylation in colorectal cancer cells and to induce apoptosis in these cells via inhibition of the PI3K-Akt survival signaling cascade ( Figure 1 ; [ 72 , 73 ]). In contrast, CBD and THC were suggested to promote PI3K/Akt signaling and thereby downregulate the expression of GSK3-β, a serine/threonine kinase and an inhibitor of the Wnt/β-catenin pathway in various glaucoma-related models [ 74 ]. However, these trends of upregulation of PI3K/Akt signaling by CBD or THC were primarily shown in non-cancerous cells (e.g., mesenchymal stem cells derived from gingiva; non-cancerous mice brain [ 74 ]) and are opposite to what was reported for cancer cells [ 72 , 73 ].…”

3D Bioprinted GelMA‐Nanoclay Hydrogels Induce Colorectal Cancer Stem Cells Through Activating Wnt/β‐Catenin Signaling

“…In canonical Wnt/β‐catenin signaling, once Wnt is bound to Wnt ligands, degradation from the Dvl‐Axin‐APC‐GSK3 complex is prevented, and active (nonphosphorylated) β‐catenin is free to translocate to the nucleus and combine with the transcription factors TCF/LEF to initiate the transcription of Wnt target genes. [ 59 ] Our findings suggested that 5‐1 hydrogels may induce and enrich CSCs through Wnt/β‐catenin signaling, which has been considered a critical signaling pathway for CSC self‐renewal. [ 8,60 ]…”

GSK3 Is a Central Player in Retinal Degenerative Diseases but a Challenging Therapeutic Target

“…In vivo activation of cannabinoid receptors in mouse brains resulted in increased GSK3 inhibition [ 131 ]. The antioxidant action of CBD is more likely mediated by NRF2 [ 132 ]. Importantly, promoting NRF2 activity through GSK3 inhibition already showed promising effects in AD [ 133 , 134 , 135 ] and PD [ 136 , 137 ], and therefore pave the way to potential treatments for oxidative stress-related retinal diseases.…”