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Membrane-active peptides across disciplines and continents: An integrated approach to find new strategies to fight bacteria, dengue virus and neurodegeneration

Final Report Summary - MEMPEPACROSS (Membrane-active peptides across disciplines and continents: An integrated approach to find new strategies to fight bacteria, dengue virus and neurodegeneration.)

Peptide-lipid interactions are critical in several biomedical matters that seem uncorrelated at a first glance. MEMPEPACROSS deals with some of these:

1) Viral hemorrhagic fever caused by dengue virus is a serious health threat to Europe, as its vector is already present in several European Countries and the virus can easily be introduced, as it recently occurred on the Madeira Island (Portugal), Nice (France) and Korcula (Croatia). The interactions with lipid systems are necessary for dengue virus assembly and can be a target for its inhibition, namely at the level of the inhibition of the interaction of the dengue virus capsid protein with intracellular lipid droplets and very low density lipoproteins, for which a promising drug lead was identified on this project.

2) Gene-encoded antimicrobial peptides (AMPs) are innate defenses to prevent colonization and infection by microbial pathogens. Most of these peptides strongly interact with lipid membranes. Their antimicrobial efficacy and the difficulty of the target organism to develop resistance make AMPs promising candidates for new generations of drugs to fight highly threatening antibiotic-resistant strains of pathogens. During this project, important findings were obtained on the mechanisms of action at the molecular level of different AMPs with selective antibacterial (e.g. rBPI21) and antimycotic (e.g. Psd1) action.

3) Peptide-membrane interactions are also relevant for neurodegenerative diseases, such as Alzheimer disease. The identification of the conditions necessary for the triggering of the disease-inducing protein aggregation and the search for strategies to inhibit these processes are the key-aspects to be addressed. At this level, the results obtained on this project pointing out to the possibility of the use of kyotorphin as an eventual biomarker for neurodegeneration and that it may be a lead compound to be used pharmacologically for neuroprotection must be highlighted.

The societal impacts of the scientific matters addressed in this project were golden opportunities for improving public awareness of Science. This project also included a strong component of Science communication and management, including development of training activities for scientists on mass media contacts, project management and fundraising, development of Communication Programs for high school students on Scientific Society Meetings, and the development of workshops to improve the formation of school teachers, inclusively on remote locations in Brazil.

In this project, the expertise of two European institutions – Institute of Molecular Medicine (Lisbon, Portugal) and Pompeu Fabra University (Barcelona, Spain) – and of three Brazilian institutions – the Federal Universities of Rio de Janeiro and Ceará, and the Oswaldo Cruz Foundation – came together with common goals and a successful concern for the: 1) improvement of the scientific state-of-the-art, 2) effective societal impact of the achievements of the project, and 3) dissemination of the project outputs among both technical and non-technical audiences.