Synaptotoxicity in Alzheimer's disease: The Wnt signaling pathway as a molecular target

Nibaldo C. Inestrosa, Lorena Varela-Nallar, Catalina P. Grabowski, Marcela Colombres

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

54 Citas (Scopus)

Resumen

Recent evidence supports a role of the Wnt pathway in neurodegenerative disorders such as Alzheimer's disease (AD). A relationship between amyloid-β-peptide (Aβ)-induced neurotoxicity and a decrease in the cytoplasmatic levels of β-catenin has been proposed. Also, the inhibition of glycogen synthase kinase (GSK-3β), a central modulator of the pathway, protects rat hippocampal neurons from Aβ-induced damage. Interestingly, during the progression of AD, it has been described that active GSK-3β is found in neuronal cell bodies and neurites, co-localizing with pre-neurofibrillary tangles observed in disease brains. Since Aβ oligomers are associated with the post-synaptic region and we have found that the non-canonical Wnt signaling modulates PSD-95 and glutamate receptors, we propose that the synaptic target for Aβ oligomers in AD is the postsynaptic region and at the molecular level is the non-canonical Wnt signaling pathway. Altogether, our evidence suggests that a sustained loss of Wnt signaling function may be involved in the Aβ-dependent neurodegeneration observed in AD brains and that the activation of this signaling pathway could be of therapeutic interest in AD.

Idioma originalInglés
Páginas (desde-hasta)316-321
Número de páginas6
PublicaciónIUBMB Life
Volumen59
N.º4-5
DOI
EstadoPublicada - 2007

Áreas temáticas de ASJC Scopus

  • Bioquímica
  • Biología molecular
  • Genética
  • Bioquímica clínica
  • Biología celular

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