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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.

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  • Authors

    Eubanks LM, Rogers CJ, Beuscher AE, Koob GF, Olson AJ, Dickerson TJ, Janda KD

    Source

    Molecular pharmaceutics 3:6 pg 773-7

    MeSH

    Acetylcholinesterase
    Alzheimer Disease
    Amyloid beta-Peptides
    Animals
    Cannabis
    Cholinesterase Inhibitors
    Dronabinol
    Electrophorus
    Mice
    Models, Biological
    Models, Molecular
    Plaque, Amyloid

    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