Our findings suggest that the GT-repeat polymorphism in the promoter region of the NEP gene or some other unknown polymorphisms, which are in a linkage disequilibrium, confer a susceptibility to late-onset AD.
No differences in genotypic and allelic frequencies of -204G/C and 159C/T polymorphisms in NEP were found between AD and control group (for -204G/C genotype: chi2 = 2.34, P > 0.05; for allele: chi2 = 2.31, P > 0.05; for 159C/T genotype: chi2 = 1.34, P > 0.05; for allele: chi2 = 0.88, P > 0.05).
Previously, we have documented that prenatal hypoxia can aggravate the cognitive impairment and Alzheimer's disease (AD) neuropathology in APP(Swe) /PS1(A246E) (APP/PS1) transgenic mice, and valproic acid (VPA) can prevent hypoxia-induced down-regulation of β-amyloid (Aβ) degradation enzyme neprilysin (NEP) in primary neurons.
Additionally, inhibition of neprilysin metabolism of amyloid-β peptides might have an effect on Alzheimer disease, age-related macular degeneration, and cerebral amyloid angiopathy.
Our results indicate that the decrease of NEP, caused by the decline of estrogen or androgen with aging, may be an important factor leading to Abeta accumulation and AD.
We have previously shown that neprilysin (NEP), the major protease which cleaves Abetain vivo, is modified by 4-hydroxy-nonenal (HNE) adducts in the brain of Alzheimer's disease patients.
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.
These data further support a role for neprilysin in regulating cerebral amyloid deposition and suggest that gene transfer approaches might have potential for the development of alternative therapies for Alzheimer's disease.
The loss of vessel-associated NEP in AD was inversely related to the severity of CAA, and analysis of cases with severe CAA showed that levels of vascular NEP were reduced to the same extent in Abeta-free and Abeta-laden vessels, strongly suggesting that the reduction in NEP is not simply secondary to CAA.
Evidence that neprilysin in the hippocampus and cerebral cortex is down-regulated with aging and from an early stage of AD development supports a close association of neprilysin with the etiology and pathogenesis of AD.
Thus, the addition of the ApoB transport domain to the secreted neprilysin generated a non-invasive therapeutic approach that may be a potential treatment in patients with AD.
Neprilysin has been implicated in the catabolism of amyloid beta peptides in the brain and as such has received considerable attention, particularly as a therapeutic target for Alzheimer's disease.
Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer's Disease.
The multifactorial causes of AD offer a variety of possible targets for gene therapy, including two neurotrophic growth factors, nerve growth factor and brain-derived neurotrophic factor, Abeta-degrading enzymes, such as neprilysin, endothelin-converting enzyme and cathepsin B, and AD associated apolipoprotein E. This review also discusses advantages and drawbacks of various rapidly developing virus-mediated gene delivery techniques for gene therapy.
This Mini-Review summarizes NEP gene transfer technologies that use viral and nonviral vectors and discusses the rationale and benefits of these delivery systems for AD treatment trials, providing a reference for basic and clinical studies on AD.
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).