A new generation of Chilean scientists explores how synapses could predict Alzheimer’s

A new generation of young Chilean scientists seeks to contribute to the understanding of the mechanisms for predicting the origin and modifying the progression of Alzheimer’s disease, one of the most widespread neurodegenerative pathologies and whose therapeutic alternatives today only slow down the progression of symptoms in a irreversible phase. .

Guided by María Soledad Matus, deputy director of the ANID Ciencia y Vida basal center, the researchers explore the processes that regulate the biology of the central nervous system with the challenge of finding the first signs of Alzheimer’s and, based on this, establishing potential strategies for change disease progression.

Nicolás Martínez Alarcón explained that the main interest of this line of research at the lab is the exploration of a new mechanism for regulating the content of synapses, structures where neurons connect and transmit information to each other .

“This would be of fundamental importance because it would allow us to know how the specific shape and content of synapses is regulated, which are the structures in which neurons transmit information from one to another. Small changes in that content in response to stimuli are one of the foundations of memory function. Today we are studying a new regulator of this process, not previously described.”

Proper synapse function is a prerequisite for nerve impulses to travel through neural networks. Without nerve impulses traveling through these networks, our brains would be “turned off.” This disconnect occurs in neurodegenerative disorders associated with aging such as Alzheimer’s disease.

The young researcher from the Fundación Ciencia y Vida, now hosted at the University of San Sebastián, pointed out that understanding how synapses shape and maintain their content could have an impact on understanding how memory is established. And, second, it could also affect how memory might be preserved under stressful conditions.

“The laboratory led by Dr. Matus, and composed of a team of young scientists, is interested in evaluating the role of new pathways for regulating synapse content in Alzheimer’s. If this is anticipated, understanding the regulation of synapse content in the central nervous system could in the future help develop strategies that allow people with the disease to retain their memories. This is why it is essential to focus on the study of the early presymptomatic phases”.

According to data managed by the Pan American Health Organization (PAHO) and the International Federation of Alzheimer’s Associations (ADI), every three seconds there is a person in the world who develops the disease and its global costs amount to a trillion dollars. . Among the conditions classified as “dementia” it is the most widespread and in Chile: about one hundred thousand people could suffer from it.

Brain blackout

Alzheimer’s disease is a brain disorder that progressively affects memory and thinking ability and, over time, the ability to perform simpler tasks. In most people with this disease, symptoms first appear later in life.

It is estimated that they affect 5-7% of over-65s and over 35% of over-85s.

At the Basal Ciencia y Vida Center, teams of Chilean researchers are working on the challenge of finding a new regulatory mechanism and revealing that it corresponds to a fundamental discovery that will allow us to understand memory and modify the progression of pathology, according to Martínez .

“Memory or that ability we can experience to evoke memories is based on the electrical activity of different regions of the brain. The current flows through different regions of the brain and if you zoom very closely, the jump of electrical currents from one neuron to another happens in very specific structures which are the synapses”.

Inside the synapse there are different types of proteins, which regulate the efficiency of the passage of electric current from one neuron to another. This regulation is extremely fine: the specific composition of proteins in synapses is a fundamental part of the brain processes leading to the acquisition of cognition that humans acquire from infancy to adulthood.

The loss of this specific composition is what leads to the weakening of these cognitive faculties as people experience aging. What happens from then on is something that still needs a deeper understanding from basic science.

The researcher comments that “in the last decade it has been described that one of the first things that happens in the brain, long before the onset of symptoms of Alzheimer’s disease, is that the synapses lose their specific composition. In fact, at the moment one of the first existing markers of the predisposition to develop Alzheimer’s is the loss of the protein composition of the synapses”.

The explorations in the Neurodegeneration Biology laboratory of the Basal Center focus precisely on this function as one of the critical elements in the entire cellular machinery that is involved in the progression of the pathology.

“We hope this discovery of our basic science will open a path for other researchers to continue pursuing projects aimed at regulating the activity of this machinery.”

From the laboratory of this baseline ANID Center, they believe that one of the therapeutic or preventive strategies would focus on the ability to intervene in the early manifestations of the disease, projecting a potential brake on its progression.

“What we are trying to do is put ourselves at the frontier of what is known about the possibilities of modifying the severity and progression of the disease,” the scientist underlined.

The disease affects 10 million people in the Americas, and according to statistics from PAHO, deaths from dementia more than doubled between 2000 and 2016, making it the fifth leading cause of death in 2016. Furthermore, it is estimated that the number of people affected will rise from the current 50 million to 152 million in 2050.

new generation of scientists

Alzheimer’s disease is the most common form of dementia and can contribute to 60-70% of cases. Contrary to popular belief, dementia is not a normal part of aging and does not exclusively affect older people. According to the PAHO, the prevalence of dementia is growing rapidly in Latin American and Caribbean (LAC) countries.

This is primarily due to the 65 percent more disability-adjusted life years (DALYs) experienced by women living in the Americas than the global figure of 60 percent. A figure that has also increased during the covid-19 crisis and its impacts in terms of social interactions and isolation of the elderly population.

Memory loss is perceived as the most common symptom, although it is a condition with multiple components: inflammatory, emotional or physical. This occurs because the critical imbalance of the pathology occurs at the biochemical level of the brain. During its progression, Alzheimer’s primarily damages the part of the brain responsible for integrating memory.

Martínez says that while it is true that the pathology has a ubiquitous effect and affects many parts of the brain, it is particularly harmful in the region of the brain responsible for memory. That is why the first thing that clearly occurs is the difficulties in remembering events that have happened to us recently (in the short and medium term), and later, as the disease progresses, the difficulties in remembering events from our deep past (in long term).

“It has to do with the specific part of the brain that Alzheimer’s affects most severely: the hippocampus, which is the region responsible for storing and integrating memory,” says the Basal Science and Life Center researcher, who stood out in this process of exploring the role that young scientists are playing in the basic science of aging in Chile.

As he commented, an internationally recognized school of neuroscience has been established in our country, thanks to extensive fieldwork in recent decades.

“That school of neuroscientists has largely focused on the study of aging. This challenge is at the center of interests and discussions which as a society call us beyond science: the idea of ​​well-being, the quality of life, the value of the elderly. It also considers what efforts and investments we must make to have better health and old age in Chile, and take actions to do so, starting with promoting the development of scientific research. Participating in it is very stimulating for young scientists”.

In his view, the contribution of basic science to the field is vital so that, at a later level, other specialists focus on developing solutions based on that prior knowledge. All in one of the greatest challenges of modern society: the change of the demographic pyramid.

“The progress that has been made in controlling the physiology of the body has caused us to live longer and longer. And we ask our nervous systems, especially our brains, which have evolved to live fewer years, to keep working overtime. It seems that the physiology of the nervous system is so complex that it is not so easy to extend its useful life, and we are reaching much older ages, but with a deteriorated nervous system. In the face of this challenge we work,” he concluded.

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