Journal of Molecular Medicine

, Volume 84, Issue 3, pp 253–258 | Cite as

The marijuana component cannabidiol inhibits β-amyloid-induced tau protein hyperphosphorylation through Wnt/β-catenin pathway rescue in PC12 cells

  • Giuseppe Esposito
  • Daniele De Filippis
  • Rosa Carnuccio
  • Angelo A. Izzo
  • Teresa Iuvone
Original Article

Abstract

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. A massive accumulation of β-amyloid (Aβ) peptide aggregates has been proposed as pivotal event in AD. Aβ-induced toxicity is accompanied by a variegated combination of events including oxidative stress. The Wnt pathway has multiple actions in the cascade of events triggered by Aβ, and drugs that rescue Wnt activity may be considered as novel therapeutics for AD treatment. Cannabidiol, a non-psychoactive marijuana component, has been recently proposed as an antioxidant neuroprotective agent in neurodegenerative diseases. Moreover, it has been shown to rescue PC12 cells from toxicity induced by Aβ peptide. However, the molecular mechanism of cannabidiol-induced neuroprotective effect is still unknown. Here, we report that cannabidiol inhibits hyperphosphorylation of tau protein in Aβ-stimulated PC12 neuronal cells, which is one of the most representative hallmarks in AD. The effect of cannabidiol is mediated through the Wnt/β-catenin pathway rescue in Aβ-stimulated PC12 cells. These results provide new molecular insight regarding the neuroprotective effect of cannabidiol and suggest its possible role in the pharmacological management of AD, especially in view of its low toxicity in humans.

Keywords

Alzheimer’s disease β-amyloid (Aβ) peptide Cannabidiol Tau protein GSK-3β PC12 cells 

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Giuseppe Esposito
    • 1
  • Daniele De Filippis
    • 1
  • Rosa Carnuccio
    • 1
  • Angelo A. Izzo
    • 1
  • Teresa Iuvone
    • 1
  1. 1.Department of Experimental Pharmacology, Faculty of PharmacyUniversity of Naples Federico IINaplesItaly

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