Role of Alzheimer's β-Amyloid on Wnt signaling

Nibaldo C. Inestrosa, Catalina Grabowski, Macarena Arrázola, Lorena Varela-Nallar, Enrique M. Toledo

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Recent evidence supports a neuroprotective role for Wnt signaling in neurodegenerative disorders such as Alzheimer's Disease. In fact, a relationship between amyloid-β-peptide induced neurotoxicity and a decrease in the cytoplasmic levels of β-catenin has been observed. Apparently, Aβ binds to the extracellular cysteine-rich domain of the Frizzled receptor inhibiting Wnt/β-catenin signaling. These studies indicate that a sustained loss of Wnt signaling function may be involved in the Aβ-dependent neurodegeneration observed in Alzheimer's brain. So far, we have demonstrated that activation of Wnt signaling protects neurons against neurotoxic injuries, including both amyloid-β fibrils and Aβ oligomers by using either lithium, an inhibitor of the glycogen synthase kinase 3β, or different Wnt ligands. In particular, the activation of non-canonical Wnt signaling was able to protect postsynaptic regions and dendritic spines against Aβ oligomers. In conclusion, the activation of the Wnt signaling pathway could be proposed as a therapeutic target for the treatment of AD.

Original languageEnglish
Title of host publicationProtein Misfolding Disorders
Subtitle of host publicationA Trip into the ER
PublisherBentham Science Publishers Ltd.
Number of pages11
ISBN (Print)9781608055753
Publication statusPublished - 2009

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


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