Age-Related Increases in PDE11A4 Protein Expression Trigger Liquid-Liquid Phase Separation (LLPS) of the Enzyme That Can Be Reversed by PDE11A4 Small Molecule Inhibitors.

ABSTRACT: PDE11A is a little-studied phosphodiesterase sub-family that breaks down cAMP/cGMP, with the PDE11A4 isoform enriched in the memory-related hippocampal formation. Age-related increases in PDE11A expression occur in human and rodent hippocampus and cause age-related cognitive decline of social memories. Interestingly, age-related increases in PDE11A4 protein ectopically accumulate in spherical clusters that group together in the brain to form linear filamentous patterns termed "PDE11A4 ghost axons". The biophysical/physiochemical mechanisms underlying this age-related clustering are not known. Here, we determine if age-related clustering of PDE11A4 reflects liquid-liquid phase separation (LLPS; biomolecular condensation), and if PDE11A inhibitors can reverse this LLPS. We show human and mou

SUBMITTER: Amurrio E 

PROVIDER: S-EPMC12190369 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature