It reversed the increase in hippocampal amyloid beta protein, phosphorylated tau protein contents together with augmentation of neprilysin level, it also diminished levels of nuclear factor kappa-B, FAS ligand, tumor necrosis factor-alpha, malondialdehyde, and acetylcholinesterase content.These findings show the protective action of telmisartan against AD-like pathological alterations.
Vascular levels of two proteins involved in Aβ clearance, ABCB1 and neprilysin, were lower in persons with AD and positively correlated with cognitive function, while being inversely correlated to vascular Aβ40.
Proteostasis analysis showed the following in both NoTg and 3xTg-AD mice: (i) increased levels of the amyloid-degrading enzyme neprilysin, (ii) reduction of the amyloidogenic secretase BACE1, and (iii) increase of proteasome protein levels and enhancement of proteasome activity.
Membrane metalloendopeptidase (MME) and insulin-degrading enzyme (IDE) are two types of proteases that could cleave beta-amyloid (Aβ) peptides generated by neuron cells of AD patients.
Thus, studies aiming to enhance neurotrophic factors and neprilysin together with neutralizing p-Tau within the central nervous system (CNS) may alleviate brain pathology in AD.
The data obtained allowed us to conclude that the decrease in the activity of the amyloid-degrading enzyme NEP, as well as a reduction in the number of labile interneuronal contacts in the hippocampus, contribute to early cognitive deficits caused by prenatal hypoxia and that there are therapeutic avenues to restore these deficits via NEP activation which could also be used for designing preventive strategies in AD.
Although the effects of neprilysin (NEP), also called CD10, on the clearance of Alzheimer's disease (AD)-associated amyloid-β (Aβ) have been reported, NEP is not made in the brain, and the mechanism for the transport of NEP to the brain has not been investigated.
The protein levels and activity of the Zn<sup>2+</sup>-dependent endopeptidase neprilysin (NEP) inversely correlate with brain Aβ levels during aging and in AD.
Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer's Disease.
Activity of neprilysin (NEP), the major protease which cleaves amyloid-β peptide (Aβ), is reportedly reduced in the brains of patients with Alzheimer's disease (AD).
Reduced expression of important Aβ-degrading enzymes in the brain, such as neprilysin (NEP) and insulin-degrading enzyme (IDE), can promote Aβ deposition in sporadic late-onset AD patients.
While the angiotensin-converting enzyme degrades amyloid-β, angiotensinconverting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer's disease dementia (AD).
We found that 5-hydroxyindolacetic acid (5-HIAA), the final metabolite of serotonin, considered until now as a dead-end and inactive product of serotonin catabolism, significantly reduces brain Aβ in the transgenic APPSWE mouse model for AD-related Aβ pathology and in the phosphoramidon-induced cerebral NEP inhibition mouse model.
In the triple transgenic AD mouse model (3xTg-AD), repeated administration of 3 and 10 mg/kg of RGFP-966 reverses pathological tau phosphorylation at Thr<sup>181</sup>, Ser<sup>202</sup>, and Ser<sup>396</sup>, increases levels of the Aβ degrading enzyme Neprilysin in plasma, decreases Aβ<sub>1-42</sub> protein levels in the brain and periphery, and improves spatial learning and memory.
Our detailed analyses, with a substantial number of brain samples, provide the first convincing evidence that DNA methylation of the NEP promoter is not involved in AD development and progression.
This study aimed to analyze the impact of HIV subtype on NEP-mediated cleavage of Aβ by comparing cerebrospinal fluid (CSF) and serum levels of NEP between HIV+ (27 patients with HIV-1B and 26 with HIV-1C), healthy HIV- controls (n = 13), and patients with Alzheimer disease (n = 24).
Tyrosine betaine remains as a starting point for the development of NEP inhibitors because of the low probability of BBB permeation and, consequently, of NEP inhibition at the Central Nervous System, which is associated to an increment in the Aβ levels and, accordingly, with a higher risk for the onset of Alzheimer's disease.
These results suggest that a decrease in the Aβ catabolic rate may be, at least in part, one of the causes for accelerated AD-like pathogenesis in DS patients if a similar event occurs in the brains, and that neprilysin activity may be regulated directly or indirectly by DYRK1A-mediated phosphorylation.