The phosphodiesterase 5 inhibitor, KJH‐1002, reverses a mouse model of amnesia by activating a cGMP/cAMP response element binding protein pathway and decreasing oxidative damage

Abstract

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.

Icariside II, a PDE5 Inhibitor, Suppresses Oxygen-Glucose Deprivation/Reperfusion-Induced Primary Hippocampal Neuronal Death Through Activating the PKG/CREB/BDNF/TrkB Signaling Pathway

“…CREB/BDNF/TrkB signaling pathway and caspase 3-dependant apoptosis pathway. Notably, PDE5 not only plays an imperative role in learning and memory function via regulating the cGMP/PKG signal pathways, thereby activating phosphorylation of CREB as previous reports have shown (Zhang et al, 2018b) but also plays a crucial role in cerebral I/R injury as evidenced by our previous study (Deng et al, 2016). In addition, PKG could induce BDNF transcription via CREB in the nucleus, and activate it downstream TrkB (Lu et al, 1999).…”

“…cGMP, an important intracellular second messenger, plays an important role in neuron physiology (Wei et al, 2002). It is reported that phosphorylation of CREB could be triggered by cGMP, thus, contributing to memory improvement (Zhang et al, 2018a). The results showed that OGD/R markedly decreased the level of cGMP and PKG activity, whereas ICS II effectively improved cGMP level and PKG activity [F (6, 14) =14.956, P < 0.001; F (6, 14) =26.428, P< 0.001] ( Figures 4A, B).…”

Icariside II, a phosphodiesterase 5 inhibitor, attenuates cerebral ischaemia/reperfusion injury by inhibiting glycogen synthase kinase‐3β‐mediated activation of autophagy

“…Thus inhibition of GSK-3β may provide neuroprotective effects against cerebral I/R-induced injury (Chuang, Wang, & Chiu, 2011). Now PDE 5 is an enzyme that specifically hydrolyses cGMP, which can trigger the activation of PKG (L. Zhang, Seo, Li, Nam, & Yang, 2018). Recently, PDE 5 has been shown to be present in human neurons and affect the survival of neurons in ischaemic stroke, suggesting that it may be a potential drug target for treating cerebral I/R injury (Teich et al, 2016).…”

Sodium tanshinone IIA sulfonate protects against Aβ‐induced cell toxicity through regulating Aβ process

“…Oxidative, nitrosative stress and inflammation in neuron can cause dysfunction of neural junction, and then induce the nervous system damage . The antioxidant enzymes were significantly decreased in AD mice . In this study, the primary indicators of oxidative and nitrosative stress were obviously increased after Aβ treatment.…”

“…36 The antioxidant enzymes were significantly decreased in AD mice. 37,38 In this study, the primary indicators of oxidative and nitrosative stress were obviously increased after IL-1β, IL-6 and TNF-α, were observed in AD brain. [39][40][41] In our study, excessive IL-1β, IL-6 and TNF-α were produced in the Aβ-treated SH-SY5Y cells.…”