Structural molecule-associated protein changes in SUMO1-deficient mice are associated with attenuated age-related anxiety-like behavior

SUMO1 is essential for normal neural function, yet its role in age-related behavioral changes remains unclear. Using open-field and three-chamber tests in adult and middle-aged female mice, the authors found that SUMO1 deletion attenuates age-related increases in anxiety-like behavior, whereas sociability is reduced independent of age. Proteomic profiling comparing middle-aged and adult SUMO1-KO mice identified 420 upregulated and 239 downregulated proteins, with enrichment in ribosomal function, synaptic signaling, extracellular matrix organization, and calcium homeostasis. Four structural molecule-associated proteins (Adora2a, Rpl14, Actg1, and Hapln2) exhibited age-related expression changes selectively in SUMO1-KO mice, as confirmed by western blot. These data indicate that SUMO1 deletion is associated with altered structural protein networks that coincide with modified anxiety-related aging trajectories. However, mechanistic links remain unresolved. Future studies using targeted pharmacological or genetic perturbations will be needed to determine whether and how these protein changes contribute to SUMO1-related behavioral alterations.