Riluzole: a therapeutic strategy in Alzheimer's disease by targeting the WNT/?-catenin pathway.

ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disease, where the etiology remains unclear. AD is characterized by amyloid-(A?) 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/?-catenin pathway is downregulated. Downregulation of WNT/?-catenin, by activation of GSK-3?-induced A?, and inactivation of PI3K/Akt pathway involve oxidative stress in AD. The downregulation of the WNT/?-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/?-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/?-catenin pathway to modulate glutamatergic pathway, oxidative stress and neuroinflammation.

SUBMITTER: Vallee A 

PROVIDER: S-EPMC7041777 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature