CBD research - Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity

    2017:When combined with its ability to target the brain and its lack of toxic side effects, CBD may represent a promising new anti-prion drug.

    Authors:

    Dirikoc S, Priola SA, Marella M, Zsürger N, Chabry J.

    Abstract:

    Prion diseases are transmissible neurodegenerative disorders

    characterized by the accumulation in the CNS of the protease-resistant
    prion protein (PrPres), a structurally misfolded isoform of its
    physiological counterpart PrPsen. Both neuropathogenesis and prion
    infectivity are related to PrPres formation. Here, we report that the
    nonpsychoactive cannabis constituent cannabidiol (CBD) inhibited PrPres
    accumulation in both mouse and sheep scrapie-infected cells, whereas
    other structurally related cannabinoid analogs were either weak
    inhibitors or noninhibitory. Moreover, after intraperitoneal infection
    with murine scrapie, peripheral injection of CBD limited cerebral
    accumulation of PrPres and significantly increased the survival time of
    infected mice. Mechanistically, CBD did not appear to inhibit PrPres
    accumulation via direct interactions with PrP, destabilization of PrPres
    aggregates, or alteration of the expression level or subcellular
    localization of PrPsen. However, CBD did inhibit the neurotoxic effects
    of PrPres and affected PrPres-induced microglial cell migration in a
    concentration-dependent manner. Our results suggest that CBD may protect
    neurons against the multiple molecular and cellular factors involved in
    the different steps of the neurodegenerative process, which takes place
    during prion infection. When combined with its ability to target the
    brain and its lack of toxic side effects, CBD may represent a promising
    new anti-prion drug.

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