Suppression of FUS aggregation by proteasome inhibitors

Proteasome inhibitor treatment suppresses ALS-associated mutant FUS aggregation in cells and primary neurons, contrasting with aggregation-promoting effects on other neurodegeneration-linked proteins.

• Why it matters: ALS involves aggregation of RNA-binding proteins like FUS, and proteasome inhibition was expected to worsen misfolded protein buildup rather than selectively protect.
• What they did: The study used proteasome inhibitor treatment in cells and primary neurons, identifying a unique transcriptional program; BAG3 mediated selective autophagy, while SAT1 induction and polyamine metabolic activity were required.
• The result: The findings reveal a protective response to proteasome inhibition that selectively suppresses FUS aggregation, suggesting a potential therapeutic strategy for FUS-ALS.

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