A Molecular Link between the Active Component of Marijuana and Alzheimer's Disease Pathology

Abstract

Alzheimer's disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer's disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients and reduce the health care costs attributable to Alzheimer's disease. Here, we demonstrate that the active component of marijuana, Delta9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid beta-peptide (Abeta) aggregation, the key pathological marker of Alzheimer's disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer's disease, THC is a considerably superior inhibitor of Abeta aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.

Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications

“…Beneficial effects in preclinical studies involved CB 1 R and/or CB 2 R, the selective activation of which was found to be effective in improving cognitive impairment, preserving neuronal cells, and preventing Aβ-induced microglial activation and the generation of proinflammatory mediators, as well as removing pathological deposits in different in vivo and in vitro models of AD [86][87][88][89][90]. In addition, beneficial effects of cannabinoids in AD may also be, at least partially, related to the activation of PPAR nuclear receptors for which certain cannabinoids may serve as ligands [88,91], whereas, in the case of some particular cannabinoids (e.g., antioxidant phytocannabinoids), they may exert some more specific effects in relation with AD pathogenesis, for example: 1) by preventing Aβ aggregation, thereby hindering plaque formation and reducing the density of neuritic plaques due to inhibition of acetylcholinesterase activity or increased expression of neprilysin, an enzyme in the Aβ degradation cascade [86,[91][92][93][94]; and 2) by inhibiting Aβ-induced tau protein hyperphosphorylation by glycogen synthase kinase-3β [82][83][84]. Some recent studies have also highlighted the interest of targeting endocannabinoid inactivation in AD, through strategies of genetic inactivation [e.g., mice deficient in monoacylglycerol lipase (MAGL) or fatty acid amide hydrolase (FAAH)] or by inhibiting these enzymes (e.g., JZL184, URB597, respectively) [95][96][97][98].…”

Study on the Physicochemical Properties of Some Commercial Soaps Available in Bangladeshi Market

“…The common alkal is utilized in soap manufacturing are potassium hydroxide (KOH) and sodium hydroxide (NaOH) also known as caustic soda [8]. It involves the putrefaction of soap by known volume of standard volumetric mineral acid solution, removal of the liberated fatty matter by heating [9].…”

Cannabinoids in Health and Disease

“…THC competitively inhibits acetylcholinesterase (AChE) and prevents AChE-induced amyloid beta-peptide (Abeta) aggregation, the key pathological marker of AD. 178 THC treatment also decreased severity of disturbed behavior, and this effect persisted during the placebo period in patients who had received THC. 179 Compared with baseline, THC led to a reduction in nocturnal motor activity.…”