Canonical Wnt signaling protects hippocampal neurons from A beta oligomers: role of non-canonical Wnt-5a/Ca2+ in mitochondrial dynamics
Alzheimer's disease (AD) is the most common type of age-related dementia. The disease is characterized by a progressive loss of cognitive abilities, severe neurodegeneration, synaptic loss and mitochondrial dysfunction. The Wnt signaling pathway participates in the development of the central nervous system and growing evidence indicates that Wnts also regulate the function of the adult nervous system. We report here, that indirect activation of canonical Wnt/beta-catenin signaling using Bromoindirubin-30-Oxime (6-BIO), an inhibitor of glycogen synthase kinase-3 beta, protects hippocampal neurons from amyloid-beta (A beta) oligomers with the concomitant blockade of neuronal apoptosis. More importantly, activation with Wnt-5a, a non-canonical Wnt ligand, results in the modulation of mitochondrial dynamics, preventing the changes induced by A beta oligomers (A beta o) in mitochondrial fission-fusion dynamics and modulates Bcl-2 increases induced by oligomers. The canonical Wnt-3a ligand neither the secreted Frizzled-Related Protein (sFRP), a Wnt scavenger, did not prevent these effects. In contrast, some of the A beta oligomer effects were blocked by Ryanodine. We conclude that canonical Wnt/beta-catenin signaling controls neuronal survival, and that non-canonical Wnt/Ca2+ signaling modulates mitochondrial dysfunction. Since mitochondrial dysfunction is present in neurodegenerative diseases, the therapeutic possibilities of the activation of Wnt signaling are evident.
|Título según WOS:||Canonical Wnt signaling protects hippocampal neurons from A beta oligomers: role of non-canonical Wnt-5a/Ca2+ in mitochondrial dynamics|
|Título según SCOPUS:||Canonical Wnt signaling protects hippocampal neurons from A? oligomers: Role of non-canonical Wnt-5a/Ca2+ in mitochondrial dynamics|
|Título de la Revista:||FRONTIERS IN CELLULAR NEUROSCIENCE|
|Editorial:||FRONTIERS MEDIA SA|
|Fecha de publicación:||2013|