Over the past few decades, the scientific community has been investing time and efforts in the search for increasingly evident and positive responses to combat one of the neurodegenerative diseases with the greatest impact worldwide.
Here, Maria Roque, a year 6 medical student, tells us that it was her contact with Neurosciences that triggered her curiosity about Alzheimer's disease, sowing the seed of knowledge in this semester of her academic career and fostering her desire to know more about the topic.
Thus, in 2018, the opportunity arose to participate in a GAPIC project, in the area of Alzheimer's, under the responsibility of the Laboratory of Professor Ana Sebastião and “the guidance of Professor Maria José Diógenes and João Gomes”. She explained that “this team had already discovered that the accumulation of Amyloid Beta (one of the main pathological features of the disease) leads to the truncation of a receptor (TrkB-FL). So, in this project, we tried to understand how the intracellular part of the receptor could affect the neuron gene expression.”
This research project is part of another of greater scope, already granted the Neurosciences Santa Casa Mantero Belard award by Santa Casa da Misericórdia, which has Professor Maria José Diógenes as lead researcher.
“Maria told me about her interest in participating in an ongoing research project. We wrote a project proposal which, fortunately, ended up being supported by the GAPIC, at FMUL. Maria participated in this work, mainly conducted by João Fonseca Gomes, supervised by me and in collaboration with Professor Francisco Enguita”, tells us Professor Maria José Diógenes.
“Alzheimer's disease, characterized by memory loss, is the most common form of dementia and has a major impact on the quality of life of the patients”, reiterated Maria Roque in approaching this research project that intends, as Professor Maria José Diógenes said, “to study ways to protect the mechanisms of endogenous neuroprotection mediated by a neurotrophin called BDNF in the context of Alzheimer's disease (AD)”, highlighting the work that has been going on over the last decade at the Institute of Pharmacology and Neurosciences of our faculty, directed by Professor Ana Sebastião, as well as at the iMM. "We have been studying the reason why BDNF loses its neuroprotective functions in the brain of patients with AD". “We were able to discover that, in this disease, the recipient responsible for the BDNF's actions is cleaved, giving rise to two fragments. One of the objectives of our work was to understand the functions of these fragments. To do this, it was necessary, in the first place, to know exactly the cleavage location of the receptors so that it was possible to overexpress the fragments in neuronal cells in order to study their function.”
Thus, João Fonseca Gomes went to Finland, where he produced the viruses necessary to allow the expression of the fragments. And back in Portugal, accompanied by Maria Roque, “proceeded to the transduction of neuronal cells, the isolation of mRNA and the study of gene expression, with the indispensable collaboration of Professor Francisco Enguita”, explains Professor Maria José Diógenes, who also told us about the results.
The data showed that "one of the fragments produced by the cleavage of BDNF receptors induces alteration of gene expression, and in vivo data show that it disturbs the memory of mice". At the moment, "the team has already developed a new compound to prevent the production of these fragments and preliminary results point to restoring the cognitive deficits present in an animal model of Alzheimer's Disease", she says.
Maria José Diógenes highlights the competence of Maria Roque in presenting a part of the results obtained in the “YES Meeting”, an international conference organized by medical students from the University of Porto, “which made us very proud”.
The research project was then presented under the title "Intracellular Fragment of BDNF Receiver, TrkB-ICD: Impact on Genetic Expression", in the scientific competition of the YES Meeting in Porto, which aims to "stimulate young people's interest in biomedical research". With this presentation, Maria won the parallel neuroscience session and the plenary session, “which resulted in a prize of €250 + €3000”. This recognition was the reinforcement of the desire to “reconcile research with clinical practice in my future as a doctor”, says Maria Roque, dedicating the last words in the comment to this achievement to thanking the team that “accompanied me and ambitioning that the discoveries in the area of neurosciences become increasingly impactful, so that we can intervene more effectively in the control of neurodegenerative diseases, whose impact at the individual, family and social levels is so negative.”
In her own words, Maria Roque shares with us what was “without a doubt an enriching experience, which enabled me to improve my critical stance, deepen my knowledge on this topic and understand the way of working in the laboratory and multidisciplinary cooperation”.
For us, this distinction is also an honour and a source of great pride, and we commend the commitment of all those involved in a research project that is both ambitious and promising.