The Wnt pathway, cell-cycle activation and β-amyloid: Novel therapeutic strategies in Alzheimer's disease?

Andrea Caricasole, Agata Copani, Alessandra Caruso, Filippo Caraci, Luisa Iacovelli, Maria Angela Sortino, Georg C. Terstappen, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

β-Amyloid protein (βAP) is thought to cause neuronal loss in Alzheimer's disease (AD). Applied to neurons in culture, βAP induces neuronal death and hyperphosphorylation of tau protein, which forms neurofibrillary tangles (NFTs) in AD brains. Neurons also undergo rapid apoptotic death following reactivation of a mitotic cycle. However, the molecular events that determine the fate of neurons challenged with βAP (apoptotic death, formation of NFTs and survival) are unclear. We discuss a scenario for the pathogenesis of AD. This links βAP-induced changes to the Wnt signaling pathway that promotes proliferation of progenitor cells and directs cells into a neuronal phenotype during brain development. We propose that βAP-mediated facilitation of mitogenic Wnt signaling activates unscheduled mitosis in differentiated neurons. Furthermore, late downregulation of Wnt signaling by βAP might lead to NFT formation. We propose that drugs that both inhibit the cell cycle and rescue Wnt activity could provide novel AD therapeutics.

Original languageEnglish
Pages (from-to)233-238
Number of pages6
JournalTrends in Pharmacological Sciences
Volume24
Issue number5
DOIs
Publication statusPublished - May 1 2003

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Fingerprint Dive into the research topics of 'The Wnt pathway, cell-cycle activation and β-amyloid: Novel therapeutic strategies in Alzheimer's disease?'. Together they form a unique fingerprint.

  • Cite this