Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/43034
Title: | Beta-amyloid interacts with and activates the long-form phosphodiesterase PDE4D5 in neuronal cells to reduce cAMP availability | Authors: | Sin, Yuan Yan Cameron, Ryan T. SCHEPERS, Melissa Macleod, Ruth Wright, Tom A. PAES, Dean van den Hove, Daniel WILLEMS, Emily Prickaerts, Jos Blair, Connor M. VANMIERLO, Tim Baillie, George S. |
Issue Date: | 2024 | Publisher: | WILEY | Source: | FEBS LETTERS, | Status: | Early view | Abstract: | Inhibition of the cyclic-AMP degrading enzyme phosphodiesterase type 4 (PDE4) in the brains of animal models is protective in Alzheimer's disease (AD). We show for the first time that enzymes from the subfamily PDE4D not only colocalize with beta-amyloid (A beta) plaques in a mouse model of AD but that A beta directly associates with the catalytic machinery of the enzyme. Peptide mapping suggests that PDE4D is the preferential PDE4 subfamily for A beta as it possesses a unique binding site. Intriguingly, exogenous addition of A beta to cells overexpressing the PDE4D5 longform caused PDE4 activation and a decrease in cAMP. We suggest a novel mechanism where PDE4 longforms can be activated by A beta, resulting in the attenuation of cAMP signalling to promote loss of cognitive function in AD. | Notes: | Baillie, GS (corresponding author), Univ Glasgow, Coll Vet Med & Life Sci, Sch Cardiovasc & Metab Hlth, Glasgow PA124EJ, Scotland. george.baillie@glasgow.ac.uk |
Keywords: | Alzheimer's disease;beta-amyloid;cyclic AMP;PDE4 | Document URI: | http://hdl.handle.net/1942/43034 | ISSN: | 0014-5793 | e-ISSN: | 1873-3468 | DOI: | 10.1002/1873-3468.14902 | ISI #: | 001216728800001 | Rights: | 2024 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
FEBS Letters - 2024 - Sin - Beta‐amyloid interacts with and activates the long‐form phosphodiesterase PDE4D5 in neuronal.pdf Until 2024-11-09 | Peer-reviewed author version | 2.92 MB | Adobe PDF | View/Open Request a copy |
auteursversie.pdf | 450.77 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.