Role of Alzheimer's β-Amyloid on Wnt signaling

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

Resultado de la investigación: Contribución a los tipos de informe/libroCapítulorevisión exhaustiva

Resumen

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.
Páginas103-113
Número de páginas11
ISBN (versión impresa)9781608055753
DOI
EstadoPublicada - 2009

Áreas temáticas de ASJC Scopus

  • Bioquímica, genética y biología molecular (todo)

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