FIGURE 3.

Reversing aberrant phase transition of nuclear RNA-binding proteins (RBPs) as a potential therapeutic option for patients with ALS/FTD. In ALS/FTD, nuclear RBPs are first mislocalized to the cytoplasm. In the cytoplasm, RBPs can undergo reversible liquid-liquid phase separation (LLPS) to form liquid condensates. In some cases, RBPs undergo aberrant phase transition into a solid-like phase where the RBPs can assemble into fibrils. Multiple methods of disassembling and disaggregating proteins are proposed, including the use of proteins, RNAs, and small molecules. These biomolecules could potentially reverse aberrant phase transition and allow for subsequent nuclear localization of the RBPs by canonical mechanisms. Created with BioRender.com.