A team of Chilean researchers has achieved promising advances in the fight against Alzheimer’s disease, after discovering a relationship between the activation of a brain pathway and the correct metabolism of sugars in the brain.

The team of researchers, led by doctors Nibaldo Inestrosa and Pedro Cisternas, of the Center for Aging and Regeneration, of the Catholic University (CARE Chile UC), managed to improve the cognitive capacity and memory in mice. The study was published recently in the Journal of Neurochemistry.

With this study, the researchers were able to determine the importance of the activation of a brain pathway called Wnt in the metabolism of glucose, a fundamental process for neurons and brain activity.

The experiments, developed in transgenic animal models, specifically seek to slow or delay Alzheimer’s disease, the most frequent disease associated to aging, which affects some 18 million people in the world and is the fourth cause of death on the planet.

The research “indicates that the activation of the Wnt pathway stimulates glucose metabolism, mainly in neurons, a very important process in the brain, an organ that requires a lot of glucose and energy for its proper functioning, especially in regions related to memory processes and learning, such as the cortex and the hippocampus,” explained Dr. Cisternas.

The brain, he said, represents 2% of body weight, but needs about the 20% of oxygen and the 25% of ATP (Adenosine 5′-triphosphate, principal molecule for storing and transferring energy in cells) of the human body.

Cisternas said that a significant aspect is that the metabolism of the glucose is diminished in almost all the neurodegenerative diseases like Alzheimer’s, Parkinson’s and Huntington’s, “what is linked to a decrease in the brain’s ability to use glucose.”

At the same time, Wnt is a mechanism formed by proteins, which is related to processes of brain formation, synapses, interaction of neurons, as well as memory and learning. The Chilean researchers explored its leading role in Alzheimer’s and other conditions, and some strategies to activate it, in order to prevent injuries and recover communication between neurons.

In Alzheimer’s disease, neurons suffer deterioration

Dr. Nibaldo Inestrosa explained that in Alzheimer’s disease, neurons suffer deterioration due to the accumulation of a type of insoluble protein called beta amyloid, which interrupts the signaling between neurons.

In this context, by rescuing the Wnt path “it is possible to recover the relationship between brain cells and prevent injuries. For all this, for us it is essential to find compounds that activate it, and that can be transformed into possible treatments to combat this pathology,” he said.

“In our last publication we observed that when we activate the Wnt pathway in our models, the cognitive response of these animals is improved, and glucose metabolism is stimulated, in addition to all the functions we previously explored,” he said.

But, “when at the same time we inject a glucose uptake inhibitor, this protective effect is lost, which means that the activation of the pathway promotes the improvement, but it is also dependent on the use of glucose and the generation of ATP.”

Based on this background, researchers are developing different strategies to activate the Wnt signaling pathway, in order to promote an improvement in the onset or progression of Alzheimer’s disease.

“We want to elaborate therapies from molecules that activate this pathway; and thus, benefit patients with Alzheimer’s, mainly allowing delaying memory loss. This could be of great impact for those affected and their family environment,” said Dr. Cisternas.

 

Source: Agencia ID