Presentation_Romeu Videira

Drug Discovery

Romeu A. Videira, Fátima Fernandes, Patrícia Valentão, Andreia P. Oliveira, M. Figueiredo González, João Bernardo, Daniela Correia, Rui Gonçalves, David M. Pereira, Paula B. Andrade (2016). Drug-Discovery. 1st Workshop: “Novel Compounds from renewable sources” LAQV-REQUIMTE 15 de Junho 2016, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Portugal

Abstract

A project idea to address the age-related degenerative diseases was presented and discussed in order to underpin a project with potential to compete for European funding.

 “Age-related Degenerative Diseases” is a large hat that covers several human pathologies that affect not only the brain (e.g. Alzheimer’s diseases, Parkinson’s diseases, Frontotemporal dementia and many others) but also the peripheral organs (e.g. Diabetes type 2, chronic kidney disease, cardiovascular diseases and skeletal muscle degeneration). Therapeutic strategies to address the problem of age-related degeneration have been dominated by a disease-specific pathophysiological vision, which is focussed on the cellular, biochemical and genetic vicissitudes specifically connected to each degenerative disease. However, these strategies have been shown to be unable to decrease the incidence of these human pathologies as well as to deflect the disease-associated degenerative progression.

In rupture with this traditional view, we propose that all age-related degenerative diseases emerge from chronic low-grade inflammation associated with mitochondrial dysfunctions and oxidative stress that are able to trigger a pathophysiological cascade with clinical manifestation differentiated according with organ, tissue and cell population that are affected during the course of disease.

Thus, an affordable health-care strategy to control age-related chronic low-grade inflammation using an integrative multi-target strategy based on natural bioactive compounds will be investigated within the project.

Natural bioactive compounds that include a set of water-soluble polyphenols, flavonoids, and naphthoquinones and algae phospholipids with high-content of n-3 PUFA (n-6 /n-3 ≤ 1), selected considering the skills and expertise of the Natural Products Research Group.

Liposomal formulations, prepared with algae phospholipids, loaded with polyphenols, flavonoids, and naphthoquinones will be used within a therapeutic and/or bifunctional foods strategies, in order:

i) To increase cell capacity to quenching ROS and other reactive species;

ii) To increase n-3/n-6 PUFA in membrane phospholipids, decreasing the production pro-inflammatory lipid mediators;

iii) To improve the fitness of IMM to allow the functional assembling of protein complexes involved in the oxidative phosphorylation, decreasing ROS release and avoiding the  NLRP3 inflammasome activation.