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Official websites use. Share sensitive information only on official, secure websites. 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 as well as reduce the health care costs attributable to Alzheimer's disease. Currently, there are four FDA-approved drugs that treat the symptoms of Alzheimer's disease by inhibiting the active site of acetylcholinesterase AChE , the enzyme responsible for the degradation of acetylcholine, thereby raising the levels of neurotransmitter in the synaptic cleft. This grid box was designed to include regions of both the catalytic site and the peripheral anionic site. Otherwise, standard docking settings were used for the AutoDock calculations, as previously detailed. Prior to use, an aliquot of the gelatin solution was diluted in water. For the assay, the solution was diluted until enzyme activity between 0. Compounds were prepared as solutions in methanol. The increase of absorbance at nm was monitored for 2 to 5 min. All assays were run in triplicate. Initial rates were determined by subtracting the average observed initial rate from the non-enzymatic reaction. The fluorescence emission spectrum was recorded between and nm, with excitation at nm. The fluorescence intensities were averaged, and the average background fluorescence of buffer only, or buffer and THC, was subtracted. The corrected fluorescence values were plotted with their standard deviation. The student's t-test function of Microsoft Excel was used to determine p values and assess statistical significance between reactions. In fact, given the proximity of the PAS to the protein channel leading to the catalytic triad active site, it is possible to block substrate entry into the active site while bound to the PAS, thus preventing the formation of an ESI complex. Thus, these studies verify our docking results and demonstrate that THC and propidium are mutually exclusive PAS inhibitors. The catalytic triad residues of AChE green and water molecules included in the docking calculations light blue spheres are shown. A Kinetic analysis of AChE inhibition by 0. It has been shown that ThT also can bind to the PAS and that this binding leads to an increase in fluorescence. Presumably, this phenomenon results from ThT serving as a molecular rotor in which fluorescence quantum yield is sensitive to the intrinsic rotational relaxation; thus, when molecular rotation is slowed by protein binding, the quantum yield of the molecule can increase dramatically. In contrast to previous studies aimed at utilizing cannabinoids in Alzheimer's disease therapy, 8 - 10 our results provide a mechanism whereby the THC molecule can directly impact Alzheimer's disease pathology. We note that while THC provides an interesting Alzheimer's disease drug lead, it is a psychoactive compound with strong affinity for endogenous cannabinoid receptors. As a library, NLM provides access to scientific literature. Mol Pharm. Published in final edited form as: Mol Pharm. Find articles by Lisa M Eubanks. Find articles by Claude J Rogers. Find articles by George F Koob. Find articles by Arthur J Olson. Find articles by Tobin J Dickerson. Find articles by Kim D Janda. PMC Copyright notice. The publisher's version of this article is available at Mol Pharm. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.

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Magazine Proprio - September 25, As of October 17, , Canadians will be able to legally smoke marijuana recreationally, a major change to Canadian legislation. Below are some steps rental building owners can take to avoid unwanted effects of the law. Landlords must send a lease modification notice to their tenants, but only starting on October 17, Tenants cannot refuse the lease modification unless they have authorization to smoke cannabis for medical reasons. If that is the case, the tenant must notify the owner of his or her refusal on these grounds within 30 days of receiving the modification notice. Landlords will be able to add a clause to their lease prohibiting cannabis smoking as soon as the federal Cannabis Act comes into effect on October 17, The version released in October will be modified and improved. Its aim was to help landlords avoid complaints from other tenants inconvenienced by the odour and second-hand smoke. The minister refused, stating that tenants who truly need therapeutic cannabis have the right to confidentiality. The Trudeau government reiterated this spring that it will not allow the provinces to prohibit at-home cannabis cultivation, as Quebec and Manitoba plan to do. Beaulieu believes that the process could take years. That is, for recreational purposes. Tenants can still grow cannabis in their apartment for medical reasons if they have valid authorization from Health Canada, as provided by the federal law currently in effect. The landlord had to contend with a tenant who was authorized by Health Canada to grow no fewer than cannabis plants for personal use! Rental buildings cannot withstand a grow operation of this size without sustaining damages. Further, unless specified in section B of the lease, converting a unit for cannabis growing purposes is considered a change in use of the premises. The amounts double for further offence. Home News Cannabis Legalization : How landlords can limit its impact Magazine Proprio - September 25, As of October 17, , Canadians will be able to legally smoke marijuana recreationally, a major change to Canadian legislation.

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