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

2017: Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity

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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