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A molecular link between the active component of marijuana and Alzheimer's disease pathology.
Mol Pharm 2006 Nov-Dec; 3(6):773-7MP

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.

Authors+Show Affiliations

Department of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17140265

Citation

Eubanks, Lisa M., et al. "A Molecular Link Between the Active Component of Marijuana and Alzheimer's Disease Pathology." Molecular Pharmaceutics, vol. 3, no. 6, 2006, pp. 773-7.
Eubanks LM, Rogers CJ, Beuscher AE, et al. A molecular link between the active component of marijuana and Alzheimer's disease pathology. Mol Pharm. 2006;3(6):773-7.
Eubanks, L. M., Rogers, C. J., Beuscher, A. E., Koob, G. F., Olson, A. J., Dickerson, T. J., & Janda, K. D. (2006). A molecular link between the active component of marijuana and Alzheimer's disease pathology. Molecular Pharmaceutics, 3(6), pp. 773-7.
Eubanks LM, et al. A Molecular Link Between the Active Component of Marijuana and Alzheimer's Disease Pathology. Mol Pharm. 2006;3(6):773-7. PubMed PMID: 17140265.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A molecular link between the active component of marijuana and Alzheimer's disease pathology. AU - Eubanks,Lisa M, AU - Rogers,Claude J, AU - Beuscher,Albert E,4th AU - Koob,George F, AU - Olson,Arthur J, AU - Dickerson,Tobin J, AU - Janda,Kim D, PY - 2006/12/5/pubmed PY - 2007/3/27/medline PY - 2006/12/5/entrez SP - 773 EP - 7 JF - Molecular pharmaceutics JO - Mol. Pharm. VL - 3 IS - 6 N2 - 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. SN - 1543-8384 UR - https://www.unboundmedicine.com/medline/citation/17140265/abstract/A_Molecular_Link_between_the_Active_Component_of_Marijuana_and_Alzheimer's_Disease_Pathology L2 - https://dx.doi.org/10.1021/mp060066m DB - PRIME DP - Unbound Medicine ER -