CB2 receptor activation also improves cognitive impairment in animal models of AD. This review discusses available data regarding the role of CB2 receptors in AD and the potential usefulness of specific agonists of these receptors against AD. Keywords: CB2 receptor, cannabinoids, Alzheimer, neuroinflammation, β-amyloid, tau, oxidative stress Go to: Overview of Alzheimer’s disease Alzheimer’s disease is an age-dependent neurodegenerative disorder characterized by slowly progressive cognitive decline with fatal outcome.

Enhanced CB2 PET binding has been reported in the brain in an animal model of AD. In addition, CB2-specific staining is also observed in tangle-like bearing neurons and in dystrophic neurites from frontal cortex in AD. Interestingly, expression levels of CB2 receptors correlate with Aβ42 levels and plaque deposition although not with cognitive status, thus suggesting that these pathogenic events induce CB2 receptor expression.

Go to: CB2 receptor as a therapeutic target in AD: evidence from experimental models During the last decade, a number of studies have provided experimental evidence about the potential therapeutic properties of compounds targeting CB2 receptors in cellular and animal models that mimic a variety of AD-related changes.

A slight reduction in soluble Aβ and plaque content has been reported in aged AD mice lacking CB2 receptors, suggesting that CB2 receptor participation in Aβ processing may vary along with the progression of the neurodegenerative process.

AD-like mice lacking CB2 receptors display the same cognitive performance as the corresponding transgenic control mice, suggesting that CB2 receptors may not play a direct role on cognition.

Go to: Conclusions and future perspectives Taken together, the experimental observations discussed in the present review indicate that AD induces CB2 receptor expression and that targeting CB2 receptors has beneficial effects in AD. Specifically, CB2 receptor agonists reduce inflammatory responses linked to Aβ production and deposition, facilitate Aβ clearance, increase cell viability in the presence of Aβ, and promote glucose uptake in brain.

CB2 receptor agonists reduce the release of pro-inflammatory molecules, facilitate Aβ clearance by promoting microglia phagocytic phenotype, reduce Aβ … Considering the evidence of pleiotropic activity and lack of undesirable psychoactive effects of CB2 receptors, compounds acting on such cannabinoid receptors represent a promising therapy against AD. Nevertheless, there is still no information regarding the efficacy or toxicity in human beings of compounds specifically targeting CB2 receptors, which might exhibit some side effects such as immune suppression.

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