Potential Use of Marine Compounds to Modulate the Ubiquitin-Proteasome System

The Ubiquitin-Proteasome System (UPS) is a major intracellular protein degradation system, highly conserved throughout life kingdoms, where the proteasome is the core. Due to its enhanced or inhibited activity, dysregulation of the UPS has undoubtedly been implicated in the pathogenesis of various diseases, including cancer and neurodevelopmental and neurodegenerative disorders. Consequently, given its crucial role in maintaining cellular homeostasis and protein quality control, targeting the different UPS components has emerged as a promising therapeutic strategy. Here, we shortly review the capability of marine-derived compounds as novel modulators of the proteasome under their peculiar features, making them attractive for future therapeutic applications. Marine compounds present in disparate organisms inhabiting oceans exhibit different biological activities and often possess specific proteasome-modulating properties. Currently, dozens of newly isolated marine-derived compounds have shown the ability to modulate proteasome activity at very low concentrations (e.g., nano- to the micro-molar range), pointing out their superior potency and efficacy and envisaging a potential future use in the clinic. Nowadays, the marine environment has represented a fruitful “spring” for identifying different unique metabolites, and to several extents, arguably, it still holds overwhelming scientific wonders to modulate the UPS.