IISER MOHALI

Abstract: Prion diseases serve as prototypes for infectious diseases transmitted by a protein, the prion protein (PrP), yet remain incompletely understood at the molecular level. Heterogeneous species of aggregated PrP can arise from its monomer. Recent investigations, including studies by our group and others, have revealed that copper ions, nucleic acids (NAs), and RNA-binding proteins (RBPs) influence the formation of recombinant PrP condensates. Uncontrolled condensation may precede pathological aggregation. Targeting aberrant phase separation of proteins associated with neurodegenerative diseases holds promise as a therapeutic strategy. Thus, comprehending how PrP's physiological ligands—such as copper ions and proteins—and potential pathological binders—such as nucleic acids—modulate intracellular phase transitions is crucial for assessing their roles in promoting toxicity and neuronal death. In this study, we present data on the interactions between the prion protein and nucleic acids, as well as the resulting heterotypic phase separation of PrP observed through diverse in vitro biophysical approaches.