Cameron, R. T., Whiteley, E., Day, J. P., Parachikova, A. I. and Baillie, G. S. (2017) Selective inhibition of phosphodiesterases 4, 5 and 9 induces HSP20 phosphorylation and attenuates amyloid beta 1-42 mediated cytotoxicity. FEBS Open Bio, 7(1), pp. 64-73. (doi: 10.1002/2211-5463.12156) (PMID:28097089) (PMCID:PMC5221464)
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Abstract
Phosphodiesterase (PDE) inhibitors are currently under evaluation as agents that may facilitate the improvement of cognitive impairment associated with Alzheimer's disease. Our aim was to determine whether inhibitors of PDEs 4,5 and 9 could alleviate the cytotoxic effects of amyloid beta 1–42 (Aβ1-42) via a mechanism involving the small heatshock protein HSP20. We show that inhibition of PDEs 4,5 and 9 but not 3 induces the phosphorylation of HSP20 which, in turn, increases the co-localisation between the chaperone and Aβ1-42 to significantly decrease the toxic effect of the peptide. We conclude that inhibition of PDE9 is most effective to combat Aβ1-42 cytotoxicity in our cell model.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Baillie, Professor George and WHITELEY, Ellanor and Cameron, Mr Ryan and Day, Dr Jonathan |
| Authors: | Cameron, R. T., Whiteley, E., Day, J. P., Parachikova, A. I., and Baillie, G. S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | FEBS Open Bio |
| Publisher: | Wiley |
| ISSN: | 2211-5463 |
| ISSN (Online): | 2211-5463 |
| Published Online: | 08 November 2016 |
| Copyright Holders: | Copyright © 2016 The Authors |
| First Published: | First published in FEBS Open Bio 7(1):64-73 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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