The effect of autophagy on brain health

22-11-2018

Source: HEUREKA
All Content under the Creative Commons Attribution-NonCommercial 4.0 International License of HEUREKA.


By Melissa Calegaro, PhD in Biomedical Sciences. Assistant Professor and Director of the Doctorate Program in Neurobiology Universidad Mayor.

I am an initial training pharmacist. However, since I started this career, the question I wanted to help answer was why our brain gets sick. In the second semester I asked to work as a volunteer in a laboratory during my free time. I wanted to learn about this organ and how to treat it in case of illness. From there I never left science, nor the questions about the brain ... that were getting deeper and deeper.

In Brazil I followed a master's degree in subjects related to Alzheimer's disease and through an international scholarship, I arrived in Chile for a Neurotoxicity congress. I was impressed by the work done here, I decided to immigrate in 2006 and apply for a PhD in Biomedical Sciences. In 2007 I started my doctorate with a CONICYT scholarship, which made it possible for me to continue in the program, of which I am very grateful.

I did the doctorate with Claudio Hetz, in a new subject for his laboratory: autophagy or "eat yourself". This is a fundamental mechanism, mainly for cells that can not be divided, like neurons, that allow us to be who we are; think, dream, talk, remember ... Today it is known that most neurodegenerative diseases have some deficiency in the autophagic pathway, related to the cause of the disease.

Chasing answers

While I was doing my doctorate, I came to the Universidad Mayor to do some classes in the Biotechnology career, through Patrício Manque, today vice-rector of research at the university. Ute, a friend of Claudio Hetz's lab, where I did my doctorate, told me about him. I wrote to him asking if there was a course in which he could participate and he called me to make a talk for Biotechnology students. The university was taking its first steps in research ... And I'm proud to have participated in these beginnings.

979/5000With this same institution as a sponsor, I was awarded a postdoctoral FONDECYT project with Dr. Manque. Here I worked with a little studied protein that was involved with autophagy, which Patricio found through bioinformatics. This analysis allows new proteins involved with some disease, in this case ELA, to be discovered and that in a traditional way would not be possible.

Finally, I settled permanently in 2013 and from there I have seen and participated in the growth of the university. New centers and with a focus directed to the generation of knowledge through the support of research, so fundamental for a country to grow.

Devouring our memories

In 2016 I finally awarded myself a FONDECYT Initiation project and started to set up my own laboratory with the support of the university. It is dedicated to the understanding of the autophagic and endocytosis processes involved in neurodegeneration.

With this knowledge, we seek to contribute with new therapeutic targets for the intervention of Alzheimer's disease and amyotrophic lateral sclerosis (ALS). For this we use complementary experimental models, such as animals with modifications in their genome (transgenic) or that "lack a gene" (knock out), in addition to in vitro cultures of human and mouse cells.

So far, our findings indicate that the autophagic pathway does not work in the same way in different neurons. This information is fundamental, since in amyotrophic lateral sclerosis and in Alzheimer's disease, for example, different neurons are affected. Since we work with very little studied proteins, it is essential to know their location and expression pattern in the tissues of interest.

A student is finishing his master's thesis in my laboratory and had the task of systematically evaluating the expression of those proteins involved in autophagy during the progression of Alzheimer's disease in an experimental mouse model. We found that one of the proteins we study increases its expression during the progression of Alzheimer's disease in the hippocampus and cerebral cortex of these mice. However, we had seen that in ELA (spinal cord), the exact opposite happens, that is, that protein decreases, but this time in the spinal cord of the mice.

Once observed the behavior of the protein in the mouse model, we went to work in in vitro models. We are currently studying, in cell culture, the molecular mechanism that could be involved in this difference and its possible implication as a therapeutic target in both diseases. All this work is developed in collaboration with colleagues from the university, who provide us with their knowledge in different areas to answer this complex question.

Many questions to answer

Some time ago, we conducted a study of doctorates in South America with Felipe Court, Director of the Center for Integrative Biology - CIB. In this analysis, we saw that there was a lack of programs that delivered tools to answer biological questions using multimodelos, in addition to preparing them for an integral career.

That is how we decided to create the doctoral program in Neurobiology. For me it was an honor, because Chile is a country with a giant experience in neurosciences, with great scientists and scientists in the area.

What we are looking for with this program is to complement the area by answering questions, such as how does the brain work? from several experimental models, such as zebrafish, fruit fly, rats or mice, cell cultures, to samples of human donors. Using different approaches, we hope that future researchers who graduate from the doctorate will be able to ask questions that help society, both from basic science and from applied science.