Portuguese scientists secure over €90,000 to study mechanisms of neuronal death in rare autoimmune disease

Understanding the cellular and biochemical changes in neurons that lead to the accumulation of neurofibrils (small fibres that aggregate within nerve cells) and ultimately to neuronal death, particularly in anti-IgLON5 disease, is the core objective of a research project led in Portugal by the University of Coimbra (UC), which has just received over 90 thousand euros in funding from the Chan Zuckerberg Initiative.

The project, entitled 'Unraveling anti-IgLON5 disease-associated tauopathy with neuroproteomics', which will run from June 2024 to December 2025, will focus specifically on anti-IgLON5 disease - a rare, poorly understood autoimmune disease with a high mortality rate. In its early stages, the disease presents as a sleep and movement disorder, and at the cellular level it leads to the formation of neurofibrillary tangles - protein aggregates within nerve cells in the brain that contribute to neurodegeneration. Researchers also hope to gain a better overall understanding of how the brain is affected in diseases characterised by neuroinflammation, sleep disorders and cognitive dysfunction.

"We have yet 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)," explains project leader Luís Ribeiro, a researcher at the UC Centre for Neuroscience and Cell Biology (CNC-UC).

In order to better understand the mechanism of these changes, the team will develop “a disease model using autoantibodies from patients with anti-IgLON5 disease”. Luís Ribeiro explains that people with the disease "develop autoantibodies against a protein on the neuronal surface - IgLON5 - which are thought to lead to the aggregation of neuronal neurofibrils and consequently to neuronal death. However, the mechanism by which this occurs is unknown. These autoantibodies are therefore an ideal tool to study this process".

This study may also help us better understand "how the brain as a whole is affected by diseases characterised by neuroinflammation, sleep disorders and cognitive impairment," Ribeiro notes, adding that in the specific case of sleep disorders, "patients with anti-IgLON5 disease have a high prevalence of this problem, suggesting that the IgLON5 protein may also play an important role in regulating sleep. Identifying the proteins that interact with IgLON5 will therefore allow us to understand the signalling pathways controlled by this protein that regulate sleep and may be impaired in tauopathies".

The Chan Zuckerberg Initiative supports researchers and their teams from different universities to collaborate on innovative and interdisciplinary approaches to address critical challenges in neurodegenerative diseases and basic neuroscience. The University of Coimbra is collaborating on this project with a team from Northwestern University (United States), led by Jeffrey Savas, also receiving over €90,000 to carry out the research.

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