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Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity.
J Neurosci 2007; 27(36):9537-44JN

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.

Authors+Show Affiliations

Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097, Centre National de la Recherche Scientifique, 06560 Valbonne, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17804615

Citation

Dirikoc, Sevda, et al. "Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons Against Prion Toxicity." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 27, no. 36, 2007, pp. 9537-44.
Dirikoc S, Priola SA, Marella M, et al. Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity. J Neurosci. 2007;27(36):9537-44.
Dirikoc, S., Priola, S. A., Marella, M., Zsürger, N., & Chabry, J. (2007). Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 27(36), pp. 9537-44.
Dirikoc S, et al. Nonpsychoactive Cannabidiol Prevents Prion Accumulation and Protects Neurons Against Prion Toxicity. J Neurosci. 2007 Sep 5;27(36):9537-44. PubMed PMID: 17804615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity. AU - Dirikoc,Sevda, AU - Priola,Suzette A, AU - Marella,Mathieu, AU - Zsürger,Nicole, AU - Chabry,Joëlle, PY - 2007/9/7/pubmed PY - 2007/10/3/medline PY - 2007/9/7/entrez SP - 9537 EP - 44 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 27 IS - 36 N2 - 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. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/17804615/Nonpsychoactive_cannabidiol_prevents_prion_accumulation_and_protects_neurons_against_prion_toxicity_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=17804615 DB - PRIME DP - Unbound Medicine ER -