Review Volume 12, Issue 3 pp 3095—3113

Riluzole: a therapeutic strategy in Alzheimer’s disease by targeting the WNT/β-catenin pathway

Alexandre Vallée 1, , Jean-Noël Vallée 2, 3, , Rémy Guillevin 1, , Yves Lecarpentier 4, ,

  • 1 DACTIM-MIS, Laboratory of Mathematics and Applications (LMA), University of Poitiers, CHU de Poitiers, Poitiers, France
  • 2 CHU Amiens Picardie, University of Picardie Jules Verne (UPJV), Amiens, France
  • 3 Laboratory of Mathematics and Applications (LMA), University of Poitiers, Poitiers, France
  • 4 Centre de Recherche Clinique, Grand Hôpital de l’Est Francilien (GHEF), Meaux, France

received: December 11, 2019 ; accepted: January 27, 2020 ; published: February 8, 2020 ;

https://doi.org/10.18632/aging.102830
How to Cite

Copyright © 2020 Vallée et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease, where the etiology remains unclear. AD is characterized by amyloid-(Aβ) protein aggregation and neurofibrillary plaques deposits. Oxidative stress and chronic inflammation have been suggested as causes of AD. Glutamatergic pathway dysregulation is also mainly associated with AD process. In AD, the canonical WNT/β-catenin pathway is downregulated. Downregulation of WNT/β-catenin, by activation of GSK-3β-induced Aβ, and inactivation of PI3K/Akt pathway involve oxidative stress in AD. The downregulation of the WNT/β-catenin pathway decreases the activity of EAAT2, the glutamate receptors, and leads to neuronal death. In AD, oxidative stress, neuroinflammation and glutamatergic pathway operate in a vicious circle driven by the dysregulation of the WNT/β-catenin pathway. Riluzole is a glutamate modulator and used as treatment in amyotrophic lateral sclerosis. Recent findings have highlighted its use in AD and its potential increase power on the WNT pathway. Nevertheless, the mechanism by which Riluzole can operate in AD remains unclear and should be better determine. The focus of our review is to highlight the potential action of Riluzole in AD by targeting the canonical WNT/β-catenin pathway to modulate glutamatergic pathway, oxidative stress and neuroinflammation

Abbreviations

AD: Alzheimer’s disease; Acetyl-coA: Acetyl-coenzyme; APC: Adenomatous polyposis coli; DSH: Disheveled; FZD: Frizzled; GK: Glucokinase; GLUT: Glucose transporter; GSK3: Glycogen synthase kinase-3; LDH: Lactate dehydrogenase; LRP 5/6: Low-density lipoprotein receptor-related protein 5/6; MCT-1: Monocarboxylate lactate transporter-1; NDs: Neurodegenerative diseases; PI3K-Akt: Phosphatidylinositol 3-kinase-protein kinase B; PFK-1: Phosphofructokinase-1; PDH: Pyruvate dehydrogenase complex; PDK: Pyruvate dehydrogenase kinase; TCF/LEF: T-cell factor/lymphoid enhancer factor; TCA: Tricarboxylic acid.