Abstract
 
Vol 49 No. 10: 853-866 [PDF] [Full Text]
 
Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer's disease
 
Alexandre Vallée1,2, Yves Lecarpentier3, Rémy Guillevin4, and Jean-Noël Vallée2,5,*

1Experimental and Clinical Neurosciences Laboratory, INSERM U1084, University of Poitiers, Poitiers, France,
2Laboratoire de Mathématiques et Applications (LMA), UMR CNRS 7348, Université de Poitiers, Poitiers, France,
3Centre de Recherche Clinique, Hôpital de Meaux, Meaux, France,
4Université de Poitiers et CHU de Poitiers, DACTIM, Laboratoire de Mathématiques et Applications, UMR CNRS 7348, SP2MI, Futuroscope, France, and
5CHU Amiens Picardie, Université Picardie Jules Verne (UPJV), Amiens, France
 

Abstract  Alzheimer's disease (AD) is a neurodegenerative disease, in which the primary etiology remains unknown. AD presents amyloid beta (Aβ) protein aggregation and neurofibrillary plaque deposits. AD shows oxidative stress and chronic inflammation. In AD, canonical Wingless-Int (Wnt)/β-catenin pathway is downregulated, whereas peroxisome proliferator-activated receptor γ (PPARγ) is increased. Downregulation of Wnt/β-catenin, through activation of glycogen synthase kinase-3β (GSK-3β) by Aβ, and inactivation of phosphatidylinositol 3-kinase/Akt signaling involve oxidative stress in AD. Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid from Cannabis sativa plant. In PC12 cells, Aβ-induced tau protein hyperphosphorylation is inhibited by CBD. This inhibition is associated with a downregulation of p-GSK-3β, an inhibitor of Wnt pathway. CBD may also increase Wnt/β-catenin by stimulation of PPARγ, inhibition of Aβ and ubiquitination of amyloid precursor protein. CBD attenuates oxidative stress and diminishes mitochondrial dysfunction and reactive oxygen species generation. CBD suppresses, through activation of PPARγ, pro-inflammatory signaling and may be a potential new candidate for AD therapy.

 

Keywords   cannabidiol, Wnt/β-catenin pathway, PPARγ, Alzheimer’s disease, PI3K/Akt pathway, oxidative stress, neuroinflammation, GSK-3β

 

Received   2017-2-14  
Accepted  
2017-4-20

 
 

* Correspondence address  Tel: +33-3-22088000; E-mail: valleejn@gmail.com

 
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