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Rôle des cellules immunitaires et effet des cannabinoïdes dans la physiopathologie des maladies à prions

Abstract : The key event in prion diseases is the conversion of the cellular prion protein (PrPc) into a pathological and proteolysis-resistant isoform, named PrPres. PrPres is responsible for both neuropathogenesis and transmissibility of the disease. The search for molecules able to inhibit its formation in the brain is potentially a therapeutic strategy. Cannabidiol, a non psycho-active component of Cannabis Sativa, inhibits PrPres formation in vitro and in vivo and significantly prolongs the survival time of prion-infected mice. Numerous studies suggest the involvement of immune cells in the uptake and transport of PrPres. Using a transgenic mouse model of transient depletion of dendritic cells, we demonstrated the involvement of these cells in the lymphoinvasion process after intra-peritoneal but not oral infection.
The physiological functions of the PrPc are poorly understood, particularly in the immune system. Finding its partners could shed light on the role of PrPc. Fluorescent probes made of recombinant PrP were produced and used to characterize the PrPc binding sites in murine splenoctytes. The binding of tracers onto B lymphocytes resulted in the activation of the MAP kinase pathway and the transient elevation of intracellular calcium concentration demonstrating the functionality of the binding. The physiological role of these interactions and the molecular nature of PrPc receptors remain to be determined.
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https://tel.archives-ouvertes.fr/tel-00317568
Contributor : Nadine Loudig <>
Submitted on : Wednesday, September 3, 2008 - 3:37:56 PM
Last modification on : Monday, October 12, 2020 - 10:27:24 AM

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Sevda Cordier-Dirikoc. Rôle des cellules immunitaires et effet des cannabinoïdes dans la physiopathologie des maladies à prions. Neurosciences [q-bio.NC]. Université Nice Sophia Antipolis, 2008. Français. ⟨tel-00317568⟩

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