Open AccessSelective inhibition of phosphodiesterases 4, 5 and 9 induces HSP20 phosphorylation and attenuates amyloid beta 1–42‐mediated cytotoxicity
Author(s) -
Cameron Ryan T.,
Whiteley Ellanor,
Day Jon P.,
Parachikova Anna I.,
Baillie George S.
Publication year - 2017
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12156
Subject(s) - cytotoxicity , phosphodiesterase , phosphorylation , peptide , cytotoxic t cell , amyloid beta , chemistry , amyloid (mycology) , pharmacology , cancer research , microbiology and biotechnology , biochemistry , biology , enzyme , in vitro , inorganic chemistry
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 (Aβ 1–42 ) 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 colocalisation between the chaperone and Aβ 1–42 to significantly decrease the toxic effect of the peptide. We conclude that inhibition of PDE9 is most effective to combat Aβ 1–42 cytotoxicity in our cell model.