WG leader: Edit Buzas

Co-WG leader: Irina Nazarenko

Aims:

In a similar vein to determining the physiological relevance of ME, data already generated by Action members on MEs in disease and deemed suitable for integrating and/or directly comparing will be co-assessed in order to determine the breadth of our collective understanding of the pathophysiological role(s) of ME. Again, subsequent studies will leverage from both the positive data and also data deemed to be negative (learn from mistakes and build on our collective strengths) to more comprehensively understanding the relevance of ME in diseases. Based on the expertise of the current participants and being realistic with timing (we cannot address all issues together!), the initial diseases considered will be cancer, allergy, autoimmunity and neurodegenerative diseases, although an open-policy is intended – both to learn from and to contribute to research arising from MEs in other diseases.

Tasks:

Integrating and critically evaluating available data on pathophysiological roles of ME

• Collecting and summarising current knowledge in ME pathophysiological and identifying substantial gaps in our understanding of ME in disease;
• Making this information available, through this COST Action, to all interested parties.

Extending existing research to advanced elucidation of their role in disease

• In relation to neurodegenerative diseases, Action participants have shown that b-amyloid peptides, causatively linked to Alzheimer’s disease, are released into the extracellular milieu and can contribute to the propagation of amyloids in the brain and formation of extracellular amyloid plaques. During this Action, the cellular aspects of the release of exosomes and the mechanism by which amyloid proteins are loaded onto the exosomal vesicles, as well as trafficking of exosomes through the brain and how exosomes contribute to the formation of amyloid plaques, will be investigated through collaborative efforts involving scientists, clinicians and industry.
• In relation to cancer, ME-HAD participants have shown evidence that dysregulation of vesicle trafficking in cancer cells contributes to tumorigenesis and that cancer cellderived MEs can transfer “aggressive” characteristics to recipient cells or serve as cancer cell immune-tolerising entities. During this Action, mechanisms involved (e.g. Rab GTPases) in regulating ME release from cancer cells; how exosomes instruct the local and distant environment, including metastatic niches; and the contents (mRNA, miRNA, lncRNA, proteins) of those MEs will be explored in in vitro, in vivo and ex vivo model systems through collaborative efforts including ME-HAD scientists, clinicians and industry.