Role of Alzheimer's β-Amyloid on Wnt signaling

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

Producción científica: Contribución a los tipos de informe/libroCapítulorevisión exhaustiva


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.

Idioma originalInglés
Título de la publicación alojadaProtein Misfolding Disorders
Subtítulo de la publicación alojadaA Trip into the ER
EditorialBentham Science Publishers Ltd.
Número de páginas11
ISBN (versión impresa)9781608055753
EstadoPublicada - 2009

Áreas temáticas de ASJC Scopus

  • Bioquímica, Genética y Biología Molecular General


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