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Researchers explore possible innovative tool in Alzheimer’s disease therapy

Currently without effective therapies, Alzheimer's disease is one of the biggest health problems worldwide, having a major economic and social impact.

A team of researchers from the Center for Neuroscience and Cell Biology (CNC) of the University of Coimbra (UC) has discovered a possible new therapeutic target for Alzheimer’s disease that could represent an important step in the treatment of this neurodegenerative disease.

It is characterized by the progressive degeneration and death of neurons, especially in the hippocampus area, the region of the brain responsible for the formation and consolidation of memories. It is believed that the loss of function of neurons in this region will be at the basis of the memory loss observed in the disease.

Thus, the study, already published in the scientific journal Molecular Therapy – Nucleic Acids, looked for microRNAs (small genetic sequences with a regulatory role in our cells) that were possible innovative therapeutic targets for Alzheimer’s disease, having filtered the microRNA-31 as promising target for this type of strategy.

This work had as main objective «to study if it would be possible to obtain, through the modulation of a specific microRNA, a beneficial effect in an animal model of Alzheimer’s disease.

We wanted to see if increasing the levels of microRNA-31 – already identified in lower amounts in the plasma of patients, compared to healthy people of the same age – would bring relevant benefits not only with regard to the histopathological characteristics of the disease, but also in terms of changes behavioral characteristics of the pathology ”, says Ana Luísa Cardoso, project coordinator.

©Paulo-Amaral

To assess the beneficial effects of microRNA-31, the team of researchers used a mouse animal model to study Alzheimer’s disease, using only females.

After injection of a genetically modified virus that forced the expression of the micro RNA-31, markers of the disease were evaluated, such as the accumulation of beta amyloid plaques (toxic clusters of a peptide, characteristic of the disease) in the animals’ brains, as well as the loss neuronal function in the hippocampus zone.

Behavioral tests were also carried out to assess whether microRNA-31 could prevent the memory loss associated with Alzheimer’s disease.

In the next phase of the study, the team will seek to understand how the use of this microRNA-31 could be useful for the development of therapeutic strategies for other neurodegenerative diseases and to better explore how this sequence exerts the protective effects observed.

It will also study the role of this microRNA in other models of the disease that are more easily transposable to humans.

This study, which also included the participation of Vítor Carmona, Elisabete Ferreiro, Joana Guedes, Pedro Cunha, Ana Maria Cardoso, Luís Pereira de Almeida, Catarina Resende de Oliveira and João Ask – also CNC researchers – and with the collaboration of João Pedro de Magalhães, a researcher at the University of Liverpool, United Kingdom, was financed by the European Regional Development Fund (ERDF), the Foundation for Science and Technology (FCT), Bial and the Marie Curie action program.

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