Re-balancing cellular fatty acid metabolism to mend the failing heart and damaged brain (R-12951)

Disturbances in lipid metabolism are increasingly being recognized as drivers of the development and progression of cardiovascular disorders (CVD) and multiple sclerosis (MS). To date, however, the exact cellular pathways and lipids involved in driving metabolic disturbances in these disorders remain poorly understood. Recently, we demonstrated that the fatty acid translocase CD36 acts as essential gatekeeper of cellular lipid metabolism in CVD and MS, with minor changes in its plasmalemmal expression having a major impact on cardiac disease states and neuropathological parameters. Our exciting preliminary data now indicate that S-palmitoylation - an understudied post-translational lipid modification - controls CD36 distribution and activity, and impacts disease pathogenesis in CVD and MS. Based on these findings, we hypothesize that disease-associated changes in CD36 S-palmitoylation underlie perturbed cellular lipid metabolism in CVD and MS. By using human IPSC-derived cell cultures and a state-of-the-art click chemistry approach, we aim to identify in this project if CD36 palmitoylation represent a novel therapeutic target to rectify disturbances in cellular metabolism in CVD and MS. Importantly, by applying a high-throughput screening platform to identify small molecules that interfere with CD36 S-palmitoylation, this study will pave the way for a clinically-relevant treatment strategy to rescue lipid disturbances in CVD and MS.

Keywords:cellular fatty acid metabolsim, damaged brain, heart

Disciplines:Lipids, Proteins, Energy metabolism, Neurosciences not elsewhere classified, Cardiology

Project type:Collaboration project