Cell-type specific delivery of autophagy inducers as a strategy to address localized autophagy impairment in disease 01/11/2023 - 31/10/2025


Autophagy is a ubiquitous physiological process that breaks down and recycles obsolete or dysfunctional cellular components. It helps cells to survive during times of nutrient deprivation and supports clearance of protein aggregates and damaged subcellular components, thereby avoiding proteotoxic stress. Impaired autophagy has been identified as a hallmark of multiple pathologies, among others cardiovascular disease and metabolic disorders. During the last years, preclinical evidence has mounted that pharmacologically inducing autophagy, could be a game-changer in the treatment of these diseases. From a safety and efficiency perspective, one might question whether systemic treatment with autophagy inducers is the optimal way to address the localized autophagy defects that are present in most of these diseases. With that respect, we propose a cell-type specific strategy for delivering autophagy inducers. More specifically, we will prepare autophagy inducers that are chemically derivatized to target two cell types that play a key role in diseases characterized by impaired autophagy: 1) vascular endothelium (atherosclerosis) and 2) hepatocytes (NAFLD/Non-alcoholic fatty liver disease). All new compounds will be thoroughly investigated in vitro and in cells. The most promising compound will be submitted to in vivo investigation in a murine model of either atherosclerosis or NAFLD.


Research team(s)

Project type(s)

  • Research Project