Exploring the therapeutic potential of mitochondrial uncouplers in the context of Alzheimer ́s disease

Objetivo temático: Our EXPLORATORY RESEARCH PROPOSAL AIMS at presenting robust preclinical experimental evidence that the direct modulation of mitochondria by mitochondrial uncouplers can be a useful tool to protect brain cells from the irreversible pathological events that occur in AD pathology.

Área Científica: Mitochondrial dysfunction

Síntese do Projeto: While mitochondrial dysfunction undeniably plays an important role in AD, evidence is lacking about the potential therapeutic benefits achieved by the modulation of mitochondrial uncoupling in disease pathophysiology. In this exploratory project, we intend to conduct a preclinical study using a differentiated cell line of human origin to assess the potential protective effects of different mitochondrial uncouplers under AD conditions. With the proposed experimental model, we intend to have a physiologically relevant system in which it will be possible to examine the interaction of two major brain cell types, neurons and astrocyte, and also to assess both aspects of neurodegeneration and neuroinflammation in the context of AD, which are intrinsically related. Uncovering these protective events and the potential diverse behaviour of different uncouplers is important from a fundamental and translational point of view as will allow to shape future studies in in vivo models of the disease. Importantly, both positive and negative results will be informative. Ultimately, the overarching goal of this exploratory project is to identify the compound with the best safety and protective profile which will advance scientific knowledge representing an important avenue to explore a new treatment perspective in AD, and possibly other mitochondria dysfunction-associated (neurodegenerative) diseases.

Área de intervenção: Alzheimer's disease

Investigador Responsável na UC: Susana Maria Batista Tieres Tomé Cardoso

Unidade Orgânica UC: Reitoria - CNC

Instituições participantes no Projeto: Universidade de Coimbra

Instituição Financiadora/Gestora: European Society for Clinical Investigation (ESCI)

Programa de Financiamento: ESCI Exploratory Research Grants 2023

Período de execução: 01/01/2024 a 30/06/2025 (18 meses)

Custo total elegível (EUR): 10 000,00 €

Apoio financeiro da UE: 10 000,00 €

Técnico do Projeto: Heidi Maria da Silva Lopes Gonçalves | heidi.goncalves@uc.pt

Contacto: 239247017