Heteronemin, a marine sponge terpenoid, targets TDP-43, a key factor in several neurodegenerative disorders

Trans-activation response DNA-binding protein of 43 kDa (TDP-43), a key factor in several neurodegenerative conditions, was discovered as a novel target of heteronemin by chemical proteomics. Combining biophysical orthogonal approaches with biological analysis, heteronemin was found to influence the binding of TDP-43-cognate nucleic acids and to modulate the TDP-43 aggregation state and its cellular localization.