Wspólnotowy Serwis Informacyjny Badan i Rozwoju - CORDIS

FP7

PRAGTO Streszczenie raportu

Project ID: 628934
Źródło dofinansowania: FP7-PEOPLE
Kraj: United Kingdom

Final Report Summary - PRAGTO (Protein aggregation and toxicity in human diseases)

Alzheimer's disease is a devastating disorder which is currently lacking therapeutic treatment, largely because of the fact that the microscopic mechanism underlying the onset and the development of the pathology is still unknown. The formation of insoluble fibrillar protein aggregates, known as amyloids, is increasingly associated with the observation of toxicity, but the relationship between these two events is largely unclear. The overall aim of this project was to increase our understanding of this connection, with the view that unravelling the key physicochemical processes underlying the disease can open unprecedented new possibilities for therapeutic treatments. In order to achieve this goal, two major innovative techniques have been developed during this project: one experimental approach, based on novel microfluidic technologies, and one theoretical analysis, based on a kinetic platform which is conventionally applied to other branches of chemistry. The application of these novel methods allowed to unravel the cascade of microscopic events of nucleation and growth underlying the formation of the insoluble aggregates as well as to identify the different modalities of intervention to inhibit the aggregation process. This result represented a key breakthrough, since it became apparent that targeting specifically different microscopic events has dramatically different consequences on the formation of the most toxic species associated with the disease. It was therefore possible to identify the best modality of intervention, and by screening different molecules we found a biological relevant molecule that is capable of targeting specifically and significantly the key step responsible for the formation of toxic species during the aggregation of the peptide Abeta42, the peptide closely associated with Alzheimer’s disease. Although this molecule does not have therapeutic relevance per se, these results revealed for the first time which target should be addressed, and we can now use this powerful platform to search for potential drug candidates that achieve this goal. The tremendous impact of the results of this project on both the scientific community and the entire society is self-evident, and it is documented by the large number of publications in major scientific journals as well as by the several articles which were reported in all major English and European newspapers following the publication of a key paper related to this project (see list of web-sites in the attachment below). For further information about this project as well as the following-up studies please email: tpjk2@cam.ac.uk or paolo.arosio@chem.ethz.ch.

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Numer rekordu: 183616 / Ostatnia aktualizacja: 2016-06-06
Źródło informacji: SESAM