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 has just won more than 90,000 euros in funding from the Chan Zuckerberg Initiative.
The project Unraveling anti-IgLON5 disease-associated tauopathy with neuroproteomics - which will run from June 2024 to December 2025 - will specifically study anti-IgLON5 disease, a rare autoimmune pathology that has been little studied and has a high mortality rate. In the early 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, leading to their degeneration. With this study, scientists also hope to gain a more general understanding of how the brain is affected in diseases characterized by neuroinflammation, sleep disorders 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)," says Luís Ribeiro, researcher at the UC Center for Neuroscience and Cell Biology.
In this context, to better understand the process of these alterations, the team is going to create "a disease model using autoantibodies obtained from patients with anti-IgLON5 disease", stresses the project leader. Luís Ribeiro explains that people with this condition "develop autoantibodies against a protein on the neuronal surface - IgLON5 - which is 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 make it possible to identify, in a more global way, "principles about how the brain is affected in general by diseases characterized by neuroinflammation, sleep disorders, and cognitive dysfunction," says the UC researcher. In the particular case of sleep disorders, patients with anti-IgLON5 disease show this type of problem very strongly and, as such, "it is believed that the IgLON5 protein may also play an important role in controlling sleep," says the project leader. Therefore, "identifying the proteins that interact with IgLON5 will make it possible to understand the signaling pathways that are controlled by this protein, which, on the one hand, may regulate sleep; and, on the other, may be compromised in tauopathies," he adds.
The funding body, the Chan Zuckerberg Initiative, supports researchers from different universities and their teams to jointly explore innovative and interdisciplinary approaches to tackling critical challenges in the fields of neurodegenerative diseases and fundamental neuroscience. UC's partner in this project is Northwestern University, from the United States of America, through the team led by Jeffrey Savas, who will also receive more than 90,000 euros to conduct the research.
At UC, the project will also involve CNC-UC researcher and professor in the Life Sciences Department of the Faculty of Science and Technology, Ana Luísa Carvalho; CNC-UC researchers Beatriz Marques, Jeannette Schmidt and Maria Ester Coutinho; and CNC-UC PhD student Beatriz Ribeiro.
Catarina Ribeiro and Luís Ribeiro
