ENdoThelial macRophage Alliance In Neuroinflammation (ENTRAIN)

Basic data for this project

Description

Over 20 million people in Europe suffer from disabling disease entities such as strokes, multiple sclerosis and Alzheimer’s but treatment is difficult and very costly. The EU-funded ENTRAIN project is bringing together 12 partner organisations from academia and industry in 9 European countries to investigate inflammatory processes in the brain and improve therapies. The project will seek to understand how endothelial cells and macrophages work together in the brain to promote health and how this interaction may be disturbed in neurological diseases. Using novel emerging technologies such as cutting-edge chemoproteomics, unique genetic and viral tools for targeting defined cell populations and high resolution intravital imaging, ENTRAIN will lay the foundations for new promising neurological therapies. Neurological diseases cause enormous suffering and a great economic burden. Almost 20 million Europeans are affected by the most frequently occurring and disabling disease entities, such as stroke, Alzheimer’s disease (AD), or multiple sclerosis (MS), and these numbers do not include the large group of rare diseases that affect the CNS. Overall, the annual costs for patient care amount to 400 billion Euros. Common features of many neurological diseases are a vascular pathology with impaired blood-brain barrier (BBB) function or with reduced blood flow and inflammatory changes. As the two are often associated, disentangling their intricate and mutual relationship is a major task for translational neuroscience that could improve the treatment of many neurological diseases. At the cellular level, key players are brain endothelial cells as the building blocks of cerebral vessels and macrophages as the main inflammatory cells of the brain. Recent discoveries indicate that endothelial cells and brain macrophages are in intimate contact and closely interact. However, there is a huge gap of knowledge regarding the specific mode and the consequences of these interactions. Therefore, in-depth analyses of the molecular mechanisms involved are essential to identify and understand key features of macrophage-endothelial cross-talk, and exploitation of this information for the development of treatments of neurological diseases. ENTRAIN will undertake this task, using novel and emerging technologies, such as cutting-edge chemoproteomics, unique genetic and viral tools for targeting of defined cell populations, and high resolution intravital imaging. By characterising the pas de deux of endothelial cells and macrophages at the functional and morphological level, we will lay the foundation for better therapies for neurological diseases. The results will impact on the understanding of neuroinflammation, but also on the rarefaction of vessels.