Selective inhibition of phosphodiesterases 4, 5 and 9 induces HSP20 phosphorylation and attenuates amyloid beta 1-42-mediated cytotoxicity
| Autor: | Ellanor L. Whiteley, Ryan T. Cameron, Anna I. Parachikova, George S. Baillie, Jon P. Day |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Amyloid beta beta amyloid Peptide Pharmacology Selective inhibition General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine cyclic GMP Cytotoxic T cell cyclic AMP Cytotoxicity Research Articles chemistry.chemical_classification biology Phosphodiesterase Alzheimer's disease Molecular biology 3. Good health 030104 developmental biology chemistry Chaperone (protein) biology.protein Phosphorylation phosphodiesterase 030217 neurology & neurosurgery Research Article heatshock protein 20 |
| Zdroj: | FEBS Open Bio |
| ISSN: | 2211-5463 |
| DOI: | 10.1002/2211-5463.12156 |
| Popis: | 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 colocalisation 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. |
| Databáze: | OpenAIRE |
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