Is Alzheimer's Disease related to Metabolic Syndrome? A Wnt Signaling Conundrum

Is Alzheimer’s Disease related to Metabolic Syndrome?
A Wnt Signaling Conundrum

Juvenal A. Ríos, Pedro Cisternas, Marco Arrese, Salesa
Barja and Nibaldo C. Inestrosa

Abstract

Alzheimer's disease (AD) is the most common cause of dementia, affecting more than 36 million people worldwide. AD is characterized by a progressive loss of cognitive functions. For years, it has been thought that age is the main risk factor for AD. Recent studies suggest that life style factors, including nutritional behaviors, play a critical role in the onset of dementia. Evidence about the relationship between nutritional behavior and AD includes the role of conditions such as obesity, hypertension, dyslipidemia and elevated glucose levels. The coexistence of some of these cardio-metabolic risk factors is generally known as metabolic syndrome (MS). Some clinical studies support the role of MS in the onset of AD. However, the cross-talk between the molecular signaling implicated in these disorders is unknown. In the present review, we focus on the molecular correlates that support the relationship between MS and the onset of AD. We also discuss relevant issues such as the role of leptin, insulin and renin-angiotensin signaling in the brain and the possible role of Wnt signaling in both MS and AD. We discuss the evidence supporting the use of ob/obmice, high-fructose diets, aortic coarctation-induced hypertension and Octodon degus, which spontaneously develops β-amyloid deposits and metabolic derangements, as suitable animal models to address the relationships between MS and AD. Finally, we examine emergent data supporting the role of Wnt signaling in the modulation of AD and MS, implicating this pathway as a therapeutic target in both conditions.

New Article with drawings: Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons

Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons

Francisco J. Muñoz^a, b, 

Juan A. Godoy^a, 

Waldo Cerpa^c, 

Inés M. Poblete^a, d, 

Juan Pablo Huidobro-Toro^a,d, 

Nibaldo C. Inestrosa^a, e

Abstract

Wnt signaling has a crucial role in synaptic function at the central nervous system. Here we evaluate whetherWnts affect nitric oxide (NO) generation in hippocampal neurons. We found that non-canonical Wnt-5atriggers NO production; however, Wnt-3a a canonical ligand did not exert the same effect. Co-administration of Wnt-5a with the soluble Frizzled related protein-2 (sFRP-2) a Wnt antagonist blocked the NO production.Wnt-5a activates the non-canonical Wnt/Ca²⁺ signaling through a mechanism that depends on Ca²⁺ release from Ryanodine-sensitive internal stores. The increase in NO levels evoked by Wnt-5a promotes the insertion of the GluN2B subunit of the NMDA receptor (NMDAR) into the neuronal cell surface. To the best of our knowledge, this is the first time that Wnt-5a signaling is related to NO production, which in turn increases NMDARs trafficking to the cell surface.

New research Article with drawings: SIRT1 Protects Dendrites, Mitochondria and Synapses from Aβ Oligomers in Hippocampal Neurons

SIRT1 Protects Dendrites, Mitochondria and Synapses from Aβ Oligomers in Hippocampal Neurons

Juan A Godoy¹, ¹Centro de Envejecimiento y Regeneración (CARE); Departamento de Biología Celular, Molecular; Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileClaudio Allard¹, ¹Centro de Envejecimiento y Regeneración (CARE); Departamento de Biología Celular, Molecular; Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileMacarena S Arrázola¹, ²Departamento de Biología, Facultad de Ciencias, Universidad de Tarapacá, Arica, ChileJuan M Zolezzi² and ¹Centro de Envejecimiento y Regeneración (CARE); Departamento de Biología Celular, Molecular; Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, ChileNibaldo C Inestrosa^1*

Aging is a major risk factor in the onset of neurodegenerative diseases, such as Alzheimer’s disease (AD). SIRT1, a β-NAD+-dependent histone deacetylase activity, holds great potential for promoting longevity, preventing against disease and increasing cell survival. We report here, that SIRT1 protects against the damage caused by Aβ oligomers at the level of synaptic contacts, dendritic branching and mitochondrial structure in cultured rat hippocampal neurons. Neurons overexpressing SIRT1 showed increased synaptic contacts, dendritic branching and preserved mitochondrial morphology, suggesting the prevention of the Aβ oligomer-mediated neurodegeneration. Such effects were not observed in neurons overexpressing a dominant negative form of SIRT1. The potential underlying signaling pathways involved in the SIRT1 neuroprotective mechanism are discussed in the context of the peroxisome proliferator-activated receptors (PPARs), peroxisome proliferator activated receptor co-activator 1α (PGC-1α), mTOR, and the Wnt signaling pathway. Our results suggest that SIRT1 modulation might well be a therapeutic agent to protect against neurodegenerative diseases, like AD.

memory

Donde se encuentra la memoria de tu ratón ????

Neuroprotection by Wnt signaling against Amyloid-beta peptide

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.

Tripartite synapse

tripartite synapse between neurons and astrocytes !

Neuron HD!

 

Do you like the neurons?, the morphology? color? transmission ?? Here is a new model of Graphique Science for you!!

Mouse alert!

The mouse in an alert state have a behavior related with a specific posture associated to processing of fear-evoking odors emitted from cat, rat, and snake require the function of sensory neurons in the vomeronasal organ

Cajal rules!

Santiago Ramón y Cajal rules!!!!!!

His pioneering investigations of the microscopic structure of the brain were original: he is considered by many to be the father of modern neuroscience. He was skilled at drawing, and hundreds of his illustrations of brain cells are still used for educational purposes today!!!

Jak-stat signaling

He regresado de un par de congresos!!,pero finalmente creé un nuevo modelo de señalización! Con ustedes la vía de Jak-stat (con una mirada simple)!

I returned from a couple of congress! but finally I create a new model of signaling. Here is the Jak-stat pathway (in a simple view).

Glutamatergic synapse

Modelo básico de sinapsis excitatoria