Team:
Mario Milani, Eloise Mastrangelo, Claudia Massa, Francesco Bonì, Elisa Fagnani
Collaborations:
Luca Muzio, Andrea Menegon (Ospedale San Raffaele), Pierfausto Seneci (UNIMI), Luciana Marinelli (UNINA), Retromer Therapeutics (USA)
This project investigated the role of the retromer complex (VPS29, VPS35, VPS26) in endosomal trafficking and its involvement in neurodegenerative diseases, where it is altered in Alzheimer’s disease and ALS. Building on our previously identified bis-1,3-phenyl guanylhydrazones with therapeutic potential in ALS, we analyzed the interaction of the lead compound 2a with the VPS35/VPS29 complex using experimental and computational approaches. In addition, we are assembling and characterizing the full retromer complex for cryo-EM studies to gain structural insight into its architecture and ligand interactions
Funding:
ARISLA, PNRR IR EBRAINS-ITALY
