G-quadruplex (G4)-destabilization: a promising strategy to curb neurodegeneration
Small molecule-mediated G-quadruplex (G4)-stabilization has been the privileged chemical biology approach to gain insights into G4 cellular biology. While the use of G4-ligands is now routine in oncology, questions arise about the relevance of the G4-stabilization in neurobiology. Indeed, we showed that G4-stabilization in neurons triggers genetic instability and premature aging (in eLife). Therefore, an alternative strategy must be investigated, an approach that relies on the use of molecular tools able to unfold G4s to fight against G4-mediated genetic defects. In a recent review (published in Cell Chemical Biology), we described the different strategies that could be implemented to unwind G4s. Now we report in the Journal of American Chemical Society on the very first prototype of a small molecule able to unfold G4 and show how this approach holds promise as an unique way to treat neurodegeneration. These results have been highlighted by the CNRS.