Function of Nogo‐A/Nogo‐A Receptor in Alzheimer's Disease

Abstract

Nogo-A is a protein inhibiting axonal regeneration, which is considered a major obstacle to nerve regeneration after injury in mammals. Rapid progress has been achieved in new physiopathological function of Nogo-A in Alzheimer's disease in the past decade. Recent research shows that through binding to Nogo-A receptor, Nogo-A plays an important role in Alzheimer's disease (AD) pathogenesis. Particularly, Nogo-A/Nogo-A receptors modulate the generation of amyloid β-protein (Aβ), which is thought to be a major cause of AD. This review describes the recent development of Nogo-A, Nogo-A receptor, and downstream signaling involved in AD and pharmacological basis of therapeutic drugs. We concluded the Nogo-A/Nogo-A receptor provide new insight into potential mechanisms and promising therapy strategies in AD.

A novel Nogo-66 receptor antagonist peptide promotes neurite regeneration in vitro

“…It has been reported that NgR1 can bind to amyloid precursor protein (APP), and investigation of human brain samples found that NgR1 may be concentrated in amyloid plaques (Park et al, 2006a). Another study showed that NgR1 may remove amyloid beta protein (Aβ) from the brain and improve spatial memory in a transgenic mouse model, suggesting that the central Aβ residues may bind to the surface of NgR1 (Park et al, 2006b;Xu et al, 2015).…”

Fasudil reduces β-amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axis

“…The Rho/ROCK pathway is downstream of NogoA/NgR. It is involved in the progression of AD via regulation of APP metabolism, Aβ generation, reduction of phosphorylated tau levels and inhibition of neuronal regeneration (Xu et al, 2015). Consistent with the previous observation, it was found here that Fasudil treatment reduces both the expression of ROCK2 and the ratio of p-ROCK2/ROCK2 in the brain of APP/PS1 transgenic mice, which is also consistent with the presence of increased synaptophysin and Gap43.…”

“…For example, one study found that the deletion of the Nogo gene improves learning and memory deficits in APP transgenic mice and restores the levels of some synaptic markers, including synaptophysin and Gap43 (Masliah et al, 2010). Furthermore, it has been suggested that Nogo-A may trigger the occurrence and development of AD by affecting Aβ metabolism and inhibiting synaptic plasticity (Xu et al, 2015).…”

“…Previous studies have shown that Nogo-A/NgR is closely related to AD's pathogenesis by regulating the metabolism of Aβ and neurodegeneration (Xu et al, 2015). Therefore, Fasudil's effect on Nogo-A in the brain was explored by immunofluorescence, Western blot and RT-PCR.…”

A Network Pharmacology Analysis to Explore the Effect ofAstragali Radix-Radix Angelica Sinensison Traumatic Brain Injury

“…NogoA, a myelin-rich membrane protein, is a potent neurite outgrowth inhibitor and noted as an inhibitor blocking axonal regrowth and plasticity after CNS (Central Nervous System) injuries [31, 32]. In the present study, a network pharmacology approach was employed to identify the active ingredients of AR-RAS and potential targets when it is utilized to treat TBI.…”