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Séminaire impromptu - Nibaldo Manuel Inestrosa Cantin "Wnt signaling and Alzheimer´s disease"

Abstract :

Wnt signaling pathway is implicate in neural development and function, including dendrite morphogenesis, axonal growth and fine-tuning of synapses, defining the synaptic plasticity of neuronal circuits. Activation of Wnt signaling regulates synaptic structure and function in hippocampal excitatory neurons, promoting the PSD-95 clustering, development of dendritic spine morphogenesis as well as the increases in glutamatergic neurotransmission. Current evidence associates Wnt dysfunction to Alzheimer disease´s (AD), namely:  β-catenin levels are reduce in AD patients carrying presenilin-1-inherited mutations, the secreted Wnt antagonist Dickkopf-1 is elevated in postmortem AD brains, and   a variant of the LRP6 is associated with late-onset AD. 

In this seminar, I will present our recent work on the biology of the Wnt signaling in the nervous system, as well as, in vivo studies on the effect of Wnt signaling in AD animal models, including the double transgenic APPswe/PS-1 mouse, and the Chilean natural model Octodon degus. Results point to a neuroprotective potential of the Wnt cascades as a therapeutic approach to control AD.

Supported by a CONICYT Basal Center of Excellence in Science and Technology (PFB 12/2007).

http://postgrado.bio.uc.cl/facultad/profesores/nibaldo-inestrosa/



Selected publications

Pathogenicity Of Lupus Anti-Ribosomal P Antibodies: Role Of Cross-Reacting Neuronal Surface P Antigen In Glutamatergic Transmission And Plasticity In A Mouse Model
Autor(es): Segovia F, Serrano F, Dyrda A, Ampuero E, Retamal C, Bravo M, Parodi J, Zamorano P, Valenzuela D, Massardo L, Van Zundert B, Inestrosa N, Gonzalez A
Año: 2015.67:1598-1610.
Ref: Segovia F, Serrano F, Dyrda A, Ampuero E, Retamal C, Bravo M, Parodi J, Zamorano P, Valenzuela D, Massardo L, Van Zundert B, Inestrosa N, González A. Pathogenicity of lupus anti-ribosomal P antibodies: Role of cross-reacting neuronal surface P antigen in glutamatergic transmission and plasticity in a mouse model. Arthritis & Rheumatology. 2015;67(6):1598-1610.

 

The Protein Oxidation Repair Enzyme Methionine Sulfoxide Reductase A Modulates A Beta Aggregation And Toxicity In Vivo
Autor(es): Minniti A, Arrazola M, Bravo-Zehnder M, Inestrosa N, Aldunate R, Ramos F
Año: 2015.22:48-62.
Ref: Minniti A, Arrazola M, Bravo-Zehnder M, Inestrosa N, Aldunate R, Ramos F. The Protein Oxidation Repair Enzyme Methionine Sulfoxide Reductase A Modulates A beta Aggregation and Toxicity In Vivo. Antioxidants & Redox Signaling. 2015;22(1):48-62.

 

How The Wnt Signaling Pathway Protects From Neurodegeneration: The Mitochondrial Scenario
Autor(es): Arrazola M, Silva C, Inestrosa N
Año: 2015.9:1-13.
Ref: Arrazola M, Silva C, Inestrosa N. How the Wnt signaling pathway protects from neurodegeneration: the mitochondrial scenario. Frontiers In Cellular Neuroscience. 2015;9:1-13.

 

Andrographolide Activates The Canonical Wnt Signalling Pathway By A Mechanism That Implicates The Non-Atp Competitive Inhibition Of Gsk-3 Beta: Autoregulation Of Gsk-3 Beta In Vivo
Autor(es): Tapia C, Schuller A, Ureta R, Mejias C, Melo F , Inestrosa N, Hancke J
Año: 2015.466:415-430.
Ref: Tapia C, Schuller A, Ureta R, Mejias C, Melo F , Inestrosa N, Hancke J. Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3 beta: autoregulation of GSK-3 beta in vivo. Biochemical Journal. 2015;466:415-430.

 

A Novel Function For Wnt Signaling Modulating Neuronal Firing Activity And The Temporal Structure Of Spontaneous Oscillation In The Entorhinal-Hippocampal Circuit
Autor(es): Oliva C, Inestrosa N
Año: 2015.269:43-55.
Ref: Oliva C, Inestrosa N. A novel function for Wnt signaling modulating neuronal firing activity and the temporal structure of spontaneous oscillation in the entorhinal-hippocampal circuit. Experimental Neurology. 2015;269:43-55.

 

Accelerating Alzheimer's Research Through 'natural' Animal Models
Autor(es): Braidy N, Poljak A, Jayasena T, Mansour H, Inestrosa N, Sachdev P
Año: 2015.28:155-164.
Ref: Braidy N, Poljak A, Jayasena T, Mansour H, Inestrosa N, Sachdev P. Accelerating Alzheimer's research through 'natural' animal models. Current Opinion In Psychiatry. 2015;28(2):155-164.