Selective inhibition of phosphodiesterases 4, 5 and 9 induces HSP20 phosphorylation and attenuates amyloid beta 1-42 mediated cytotoxicity

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)

[img]
Preview
Text
130948.pdf - Published Version
Available under License Creative Commons Attribution.

1MB

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 Day, Dr Jonathan and WHITELEY, Ellanor and Cameron, Mr Ryan
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 > Institute of Cardiovascular and Medical Sciences
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

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
500152Doctoral Training Grant 2009-15Timothy PalmerBiotechnology and Biological Sciences Research Council (BBSRC)BB/F016735/1RI CARDIOVASCULAR & MEDICAL SCIENCES