MEMPEPACROSS

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

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 Obiettivo del progetto (Objective)

'Peptide-lipid interactions are critical in several biomedical matters that seem uncorrelated at a first glance. MEMPEPACROSS deals with some of these: 1) Lipid membrane-interactions are the key for the understanding of dengue virus assembly and can constitute a target for its inhibition. Viral hemorrhagic fever caused by dengue virus is a serious threat to Europe, as its vector is already present in several European Countries and the virus can easily be introduced. 2) Gene-encoded antimicrobial peptides (AMPs) are innate defenses to prevent colonization and infection by microbial pathogens. Most 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. 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. The societal impacts of the scientific matters to be addressed are golden opportunities to improve public awareness of Science. The project includes a strong component of Science communication and management. The expertises 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 – will come together with common goals and a 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.'

Introduzione (Teaser)

Brazilian, Portuguese and Spanish scientists joined forces to study key interactions among peptides and lipids in various biomedical processes.

Descrizione progetto (Article)

The interaction between peptides and lipids is of outmost significance in pathological conditions such as viral infection, antimicrobial defence and neurodegenerative disorders. The scope of the EU-funded MEMPEPACROSS project was to understand how such interactions lead to different diseases and to find ways to address it.

In particular, MEMPEPACROSS scientists investigated three different situations where peptide-lipid interaction is important. The first one was in the case of dengue virus, the causative agent of viral haemorrhagic fever and a possible threat to many European countries. Virus assembly requires the association of capsid proteins with intracellular lipid droplets and very low density lipoproteins, rendering this interaction a potential antiviral target.

Another situation where interaction with lipids is important is in the case of gene-encoded antimicrobial peptides (AMPs). AMPs constitute an innate immune response to prevent colonisation and infection by microbial pathogens. Pathogens are unable to resist AMPs, rendering them promising candidates for new generations of drugs especially against antibiotic-resistant microbes. During the project, the molecular mechanisms of different AMPs with selective antibacterial and antimycotic activity were unveiled.

Furthermore, researchers studied the peptide-membrane interactions in Alzheimer's disease and how they could trigger neurodegeneration. They identified kyotorphin as a biomarker for this condition and its putative role as a neuroprotective agent.

Collectively, the collaborative work of the MEMPEPACROSS consortium underscored the importance of peptide-lipid interactions and suggested ways of modulating it for therapeutic purposes.