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Fig. 9 | Molecular Neurodegeneration

Fig. 9

From: Synaptic and memory dysfunction induced by tau oligomers is rescued by up-regulation of the nitric oxide cascade

Fig. 9

oTau effect on the NO signaling cascade. Left panel shows the cascade under physiological conditions. NO is produced by the enzyme nitric oxide synthase (NOS) that converts L-arginine into L-citrulline. NO activates soluble guanilyl cyclase (sGC), which produces cyclic guanosine monosphosphate (cGMP) from guanosine triphosphate (GTP). cGMP is degraded into 5′-GMP by phosphodiesterase 5 (PDE5). The increase of cGMP levels activates cGMP-dependent protein kinase (PKG), which induces phosphorylation of cAMP-responsive element binding (CREB) and enhancement of synaptic plasticity and memory. In the presence of oTau (central panel), phosphorylation of CREB is reduced as the signaling cascade is down regulated (shown by narrower arrows), leading to an impairment of synaptic plasticity and memory processes. Treatment with PDE5 inhibitors (right panel) rescues the levels of cGMP leading to increased CREB phosphorylation and normal synaptic plasticity and memory

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