Alzheimer is an age-dependent neurodegenerative process distinct from normal aging and characterized morphologically by the presence of senile plaques, mainly composed of different species of fibrillar β-amyloid (Aβ) produced by the cleavage of the Aβ precursor protein (APP) due to β- and γ-secretases, and by the presence of neurofibrillary tangles, mostly composed of various isoforms of hyper-phosphorylated and nitrated tau protein (Duyckaerts and Dickson, 2011; Ferrer, 2012). One tendency of opinion proposes that Aβ triggers plaque formation, tau hyper-phosphorylation, and disease progression (Hardy, 2009).
Ref: Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic. Frontiers in Pharmacology (5 March 2014) | DOI: 10.3389/fphar.2014.00037
The limited effectiveness of current therapies against Alzheimer’s disease (AD) highlights the need for intensifying research efforts devoted to developing new agents for preventing or retarding the disease process. During the last few years, targeting the endogenous cannabinoid system has emerged as a potential therapeutic approach to treat Alzheimer. The endocannabinoid system is composed by a number of cannabinoid receptors, including the well-characterized CB1 and CB2 receptors, with their endogenous ligands and the enzymes related to the synthesis and degradation of these endocannabinoid compounds. Several findings indicate that the activation of both CB1 and CB2 receptors by natural or synthetic agonists, at non-psychoactive doses, have beneficial effects in Alzheimer experimental models by reducing the harmful β-amyloid peptide action and tau phosphorylation, as well as by promoting the brain’s intrinsic repair mechanisms. Moreover, endocannabinoid signaling has been demonstrated to modulate numerous concomitant pathological processes, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress. The present paper summarizes the main experimental studies demonstrating the polyvalent properties of cannabinoid compounds for the treatment of AD, which together encourage progress toward a clinical trial.