The phosphodiesterase 5 inhibitor, KJH-1002,

Title
The phosphodiesterase 5 inhibitor, KJH-1002,
Authors
남길수양현옥장리준서재홍리후안
Issue Date
2018-08
Publisher
British journal of pharmacology
Citation
VOL 175, NO 16-3360
Abstract
Background and Purpose Inhibition of PDE5 improves synaptic plasticity and memory via enhancing cGMP expression, thus activating the cGMP/cAMP response element binding protein (CREB) signalling pathway. This study investigated the effects of a PDE5 inhibitor on scopolamine‐ induced cognitive dysfunction, using memory‐ related behavioural tests and biochemical assays. Experimental Approach In mice were pretreated with PDE5 inhibitor, amnesia was induced by scopolamine. The learning and memory abilities of mice were tested using the Morris water maze test, the Y‐ maze test, the passive avoidance test and the novel object recognition test in sequence. Expression of memory‐ related bio‐ molecules and oxidative stress parameters in brain tissue were measured using Western blot and spectrophotometry respectively. Key Results KJH‐ 1002, a novel and potent inhibitor of PDE5 (IC50 0.059 ± 0.04 nmol·L− 1), was synthesized. In the behavioural tests, it markedly improved the memory performance impaired by scopolamine, indicating a restoration of cognitive function in the mice. Moreover, KJH‐ 1002 increased cGMP levels in the cortex and the scopolamine‐ reduced expression of phosphorylated CREB, Levels of ERK 1/2, Akt and brain‐ derived neurotrophic factor in the cortex and hippocampus were restored by KJH‐ 1002 treatment. In addition, KJH‐ 1002 administration increased the activities of SOD, glutathione peroxidase and glutathione reductase, and decreased the level of malondialdehyde. Conclusion and Implications KJH‐ 1002 restored cognitive function in scopolamine‐ induced amnesia mice by activating the cGMP/CREB signalling pathway and attenuating oxidative stress. The beneficial effects of KJH‐ 1002 on cognition indicate its potential as a therapeutic candidate for Alzheimer's disease.
URI
http://pubs.kist.re.kr/handle/201004/67896
ISSN
0007-1188
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE