New paper with drawings: Canonical Wnt Signaling New Paper with drawings!: Protects Hippocampal Neurons from Aβ Oligomers: Role of Non-Canonical Wnt-5a/Ca2+ in Mitochondrial Dynamics

Canonical Wnt Signaling Protects Hippocampal Neurons from Aβ Oligomers: Role of Non-Canonical Wnt-5a/Ca2+ in Mitochondrial Dynamics

Carmen Silva-Alvarez1, Macarena Arrazola2, Juan A. Godoy1, Daniela Ordenes1 and Nibaldo C. Inestrosa1, 2*
1Cell and Molecular Biology, Pontifical Catholic University of Chile, Chile
2Cell and Molecular Biology, Pontifical Catholic University of Chile, Chile

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/β-catenin signaling using Bromoindirubin-30-Oxime (6-BIO), an inhibitor of glycogen synthase kinase-3β, protects hippocampal neurons from amyloid-β (Aβ) 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, prevents changes induced by Aβ oligomers 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 Aβ oligomer effects were blocked by Ryanodine. We conclude that canonical Wnt/β-catenin signaling controls neuronal survival, and that non-canonical Wnt/Ca2+ signaling controls mitochondrial dysfunction. To our knowledge, this is the first report showing that activation of non-canonical Wnt-5a/Ca2+signaling prevents Aβ oligomer neurotoxicity. Since mitochondrial dysfunction is present in neurodegenerative diseases, the therapeutic possibilities of the activation of Wnt signaling are evident.

Review: Wnt Signaling Roles on the Structure and Function of the Central Synapses: Involvement in Alzheimer’s Disease

Review with drawings accepted !  Click Review Here !!

This is a old version of drawings of Graphique-science, but now are coming new versions!

 Wnts compromise a large family of secreted glycoproteins that have shown to be part of the signaling molecules that regulate several aspects of development such as axis formation and midbrain development [1, 2]. In mammals at least 19 Wnt members have been found. The interaction of a Wnt protein with members of the Frizzled (Fz) family of seven-pass transmembrane cell-surface receptors triggers the activation of the Wnt signaling pathway . In human and mice, 10 members of the Fz family have been identified. In addition, receptor-like tyrosine kinase (Ryk) and receptor tyrosine kinase-like orphan receptor (Ror2) have been identified as alternative Wnt receptors [6-8]. Different Wnt signaling cascades are activated downstream the Wnt receptors, identified as Wnt/β-catenin or canonical pathway, and β-catenin-independent or non-canonical pathways. The canonical pathway involves the transcription of Wnt target genes, while activation of non-canonical Wnt pathways may induce either an increase in intracellular calcium concentration or activation of the c-Jun-N-terminal kinase (JNK) cascade.

Wnt signaling / signalisation Wnt

New model proposed for Canonical Wnt signaling that depend of the accumulation of beta-catenin for the transcript Wnt target genes.


Nouveau modèle proposé pour la signalisation Wnt canonique qui dépendent de l'accumulation de bêta-caténine pour les gènes transcrits les cibles de Wnt.