More than 90 thousand euros to investigate processes that lead to neuronal death in rare autoimmune disease

Understanding the cellular and biochemical changes that occur in neurons and that lead to the accumulation of neurofibrils (small fibers that accumulate inside nerve cells) leading to neuronal death, particularly in anti-IgLON5 disease, is the central objective of a research project led in Portugal by the University of Coimbra (UC), which will receive more than 90 thousand euros in funding from the Chan Zuckerberg Initiative.

The Unraveling anti-IgLON5 disease-associated tauopathy with neuroproteomics project – which will be ongoing between June 2024 and December 2025 – will study more specifically the anti-IgLON5 disease, a rare autoimmune pathology, very little studied and with a high rate of mortality. In the initial stages, it manifests itself as a sleep and movement disorder, in which, at the cellular level, there is an accumulation of neurofibrils, which consist of protein aggregates inside neurons, which leads to their degeneration. With this study, scientists also hope to understand more generally how the brain is affected in diseases characterized by neuroinflammation, sleep disturbances and cognitive dysfunction.

“Until now it has not been possible to understand the initial biochemical and cellular changes that lead to neurodegeneration in tauopathies (neurodegenerative diseases such as Alzheimer’s, Parkinson’s and anti-IgLON5 diseases)”, contextualizes the researcher from the UC Center for Neuroscience and Cell Biology (CNC-UC), Luís Ribeiro.

In this context, to better understand the process of these changes, the team will create “a disease model in which they will use autoantibodies obtained from patients with anti-IgLON5 disease”, highlights the project leader. Luís Ribeiro explains that people with this pathology “they develop autoantibodies against a neuronal surface protein – IgLON5 –, which are thought to lead to the formation of neuronal neurofibrils and, consequently, neuronal death, but the mechanism is not known. These autoantibodies therefore provide us with the ideal tool to study these mechanisms.”

In addition to understanding these mechanisms, this research may allow us to identify, in a more global way, “principles about how the brain is affected in general by diseases characterized by neuroinflammation, sleep disturbances, and cognitive dysfunction”, advances the UC researcher. In the particular case of sleep disorders, patients with anti-IgLON5 disease present this type of problem in a very pronounced way and, as such, “it is believed that the IgLON5 protein may also have an important role in sleep control”, says the project leader. That’s why, “identifying the proteins that interact with IgLON5 will allow us to understand the signaling pathways that are controlled by this protein, which, on the one hand, may regulate sleep; and, on the other hand, they may be involved in tauopathies”, adds.

The funding entity, the Chan Zuckerberg Initiative, supports researchers from different universities and their teams to jointly explore innovative and interdisciplinary approaches to address critical challenges in the fields of neurodegenerative diseases and fundamental neuroscience. UC’s partner in this project is Northwestern University, in the United States of America, through the team led by Jeffrey Savas, who will also receive more than 90 thousand euros to conduct the research.

At UC, the project will also involve the CNC-UC researcher and professor at the Department of Life Sciences at the Faculty of Science and Technology, Ana Luisa Carvalho; CNC-UC researchers, Beatriz Marques, Jeannette Schmidt and Maria Ester Coutinho; and CNC-UC PhD student, Beatriz Ribeiro.

Coimbra University