Title

The novel histone de acetylase 6 inhibitor, MPT0G211, ameliorates tau phosphorylation and cognitive deficits in an Alzheimer's disease model.

Journal

Cell death & disease

Volume

9

Issue

None

Pages

655

Date

2018-05-29

Authors

Fan SJ | Huang FI | Liou JP | Yang CR

This study aimed to investigate the protective effects and mechanism of the novel HDAC6 inhibitor, MPT0G211, using an AD model. Our results indicated that MPT0G211 significantly reduced tau phosphorylation and aggregation, the processes highly correlated with the formation of NFTs. This HDAC6 inhibitory activity resulted in an increase in acetylated Hsp90, which decreased Hsp90 and HDAC6 binding, causing ubiquitination of phosphorylated tau proteins. In addition, a significant increase of phospho-glycogen synthase kinase-3β (phospho-GSK3β) on Ser9 (the inactive form) through Akt phosphorylation was associated with the inhibition of phospho-tau Ser396 in response to MPT0G211 treatment.

These results clearly indicated that MPT0G211 can penetrate the BBB, where it potentially ameliorates learning and memory deficits.

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