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Brief Article
A Molecular Link between the Active Component of Marijuana and Alzheimer's Disease Pathology
Departments of Chemistry, Immunology, and Molecular Biology, Molecular and Integrated Neurosciences Department, The Skaggs Institute for Chemical Biology, and Worm Institute for Research and Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037
Mol. Pharm. , 2006, 3 (6), pp 773–777
DOI: 10.1021/mp060066m
Publication Date (Web): August 9, 2006
Copyright © 2006 American Chemical Society
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, Δ9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid β-peptide (Aβ) 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 Aβ aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.
Keywords: Cannabinoids; Alzheimer's disease; acetylcholinesterase
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