Fiche publication
Date publication
janvier 2020
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr HERAULT Yann
Tous les auteurs :
Guyot AC, Leuxe C, Disdier C, Oumata N, Costa N, Roux GL, Fernandez-Varela P, Duchon A, Charbonnier JB, Herault Y, Pavoni S, Galons H, Andriambeloson E, Wagner S, Meijer L, Lund AK, Mabondzo A
Lien Pubmed
Résumé
Neurodegenerative diseases, including Alzheimer's and Parkinson's disease, are characterized by increased protein aggregation in the brain, progressive neuronal loss, increased inflammation, and neurogenesis impairment. We analyzed the effects of a new purine derivative drug, PDD005, in attenuating mechanisms involved in the pathogenesis of neurodegenerative diseases, using both in vivo and in vitro models. We show that PDD005 is distributed to the brain and can rescue cognitive deficits associated with aging in mice. Treatment with PDD005 prevents impairment of neurogenesis by increasing sex-determining region Y-box 2, nestin, and also enhances synaptic function through upregulation of synaptophysin and postsynaptic density protein 95. PDD005 treatment also reduced neuro-inflammation by decreasing interleukin-1β expression, activation of astrocytes, and microglia. We identified prohibitin as a potential target in mediating the therapeutic effects of PDD005 for the treatment of cognitive deficit in aging mice. Additionally, in the current study, glycogen synthase kinase appears to attenuate tau pathology.
Référence
Sci Rep. 2020 Jan 24;10(1):1143
