| First Author | Sin YY | Year | 2024 |
| Journal | FEBS Lett | Volume | 598 |
| Issue | 13 | Pages | 1591-1604 |
| PubMed ID | 38724485 | Mgi Jnum | J:359547 |
| Mgi Id | MGI:7787225 | Doi | 10.1002/1873-3468.14902 |
| Citation | Sin YY, et al. (2024) Beta-amyloid interacts with and activates the long-form phosphodiesterase PDE4D5 in neuronal cells to reduce cAMP availability. FEBS Lett 598(13):1591-1604 |
| abstractText | 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 (Abeta) plaques in a mouse model of AD but that Abeta directly associates with the catalytic machinery of the enzyme. Peptide mapping suggests that PDE4D is the preferential PDE4 subfamily for Abeta as it possesses a unique binding site. Intriguingly, exogenous addition of Abeta 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 Abeta, resulting in the attenuation of cAMP signalling to promote loss of cognitive function in AD. |
