Title

Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling.

Journal

Nature medicine

Volume

22

Issue

None

Pages

46-53

Date

2016-01-01

Authors

Clelland CL | Duff KE | Emrani S | Goldberg AL | Kukushkin NV | Myeku N | Yu WH

Rolipram is a specific phosphodiesterase type 4 (PDE4) inhibitor that increases cAMP levels in multiple tissues in vivo. The chymotrypsin-like activity of the 26S proteasomes in crude extracts was elevated after administration of db-cAMP or rolipram but was blocked by epoxomicin

PKA stimulation attenuated proteasome dysfunction, probably through proteasome subunit phosphorylation resulting in lower levels of aggregated tau and improvements in cognitive performance.

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