Your search for: 'author:("Wang, Deng-Shun")' has returned 4 results. (0.025s) Save search

Authors: Wang, Rui | Malter, James S. | Wang, Deng-Shun

Article Type: Research Article

Abstract: As one of the dominant amyloid-β peptide (Aβ) proteases, neprilysin (NEP) plays a crucial role in maintaining a physiologic balance between Aβ production and catabolism. We have previously shown that NEP is modified by 4-hydroxynonenal (HNE) adducts, resulting in decreased activity in the brain of AD patients and cultured cells. In order to determine whether antioxidants can rescue NEP, SH-SY5Y cells were treated with HNE or Aβ, together with N-acetylcysteine for 24 hours, prior to analysis of NEP protein levels, activity, and oxidative modifications. Intracellular NEP developed HNE adducts after 24 hours of HNE or Aβ treatment as determined by …immunoprecipitation, immunoblotting, and double immunofluorescence staining. N-acetylcysteine at 10 to 100 μM alleviated HNE adduction after HNE or Aβ treatment. In keeping with previous reports, HNE-modified NEP showed decreased catalytic activity. The present study demonstrates that antioxidants can be used to spare NEP from oxidative modification, suggesting a potential mechanism underlying the neuroprotective effects of antioxidants in aging or Alzheimer's disease. Show more

Keywords: Alzheimer's disease, amyloid-β, antioxidant, degradation, 4-hydroxynonenal, N-acetylcysteine, neprilysin, oxidative stress

DOI: 10.3233/JAD-2010-1226

Citation: Journal of Alzheimer's Disease, vol. 19, no. 1, pp. 179-189, 2010

Authors: Wang, Rui | Wang, Suqing | Malter, James S. | Wang, Deng-Shun

Article Type: Research Article

Abstract: The cerebral accumulation of amyloid-β (Aβ) is a consistent feature of and likely contributor to the development of Alzheimer's disease (AD). In addition to dysregulated production, increasing experimental evidence suggests reduced catabolism plays an important role in Aβ accumulation. Although endothelin converting enzyme (ECE) and insulin degrading enzyme (IDE) degrade and thus contribute to regulating the steady-state levels of Aβ, how these enzymes are regulated remain poorly understood. In this study, we investigated the effects of 4-hydroxy-nonenal (HNE) and Aβ on the expression and activity of ECE-1 and IDE in human neuroblastoma SH-SY5Y cells. Treatment with HNE or Aβ upregulated …ECE-1 mRNA and protein, while IDE was unchanged. Although both ECE-1 and IDE were oxidized within 24 h of HNE or Aβ treatment, ECE-1 catalytic activity was elevated while IDE specific activity was unchanged. The results demonstrated for the first time that both ECE-1 and IDE are substrates of HNE modification induced by Aβ. In addition, the results suggest complex mechanisms underlying the regulation of their enzymatic activity. Show more

Keywords: Alzheimer's disease, amyloid-β, degradation, endothelin converting enzyme, 4-hydroxy-nonenal (HNE), insulin degrading enzyme, oxidative stress

DOI: 10.3233/JAD-2009-1066

Citation: Journal of Alzheimer's Disease, vol. 17, no. 3, pp. 489-501, 2009

Authors: Wang, Suqing | Simon, Brook P. | Bennett, David A. | Schneider, Julie A. | Malter, James S. | Wang, Deng-Shun

Article Type: Research Article

Abstract: Pin1 protein, a peptidyl-prolyl cis-trans isomerase plays an important regulatory role in neuronal function. Recent studies indicate that Pin1 may promote the dephosphorylation of tau and restore its ability to bind to and polymerize microtubles. Previous studies on postmortem human brains showed that Pin1 is down-regulated in advanced Alzheimer's disease (AD) brains compared to age-matched non-demented controls. Because AD is a slowly progressive disease with a preclinical period that can last years, the abundance and regulatory function of Pin1 may vary on the course of the disease. In order to evaluate the potential contribution of Pin1 to AD pathogenesis, levels …of mRNA, protein and isomerase activity of Pin1 and phosphorylated tau from postmortem brains of 10 persons with mild-cognitive impairment (MCI), 10 with AD and 10 age-matched no cognitive impairment (NCI) were measured. The relationship between Pin1 and phosphorylated tau as well as clinical and cognitive data were analyzed. The results indicated that Pin1 activity in MCI and AD were significantly higher than in NCI. Phosphorylated tau in MCI and AD was also higher than in NCI group. The positive correlation trend in MCI and the robust correlation in AD between Pin1 activity and phosphorylated tau implies that increasing phosphorylated tau during AD pathogenesis may induce the compensatory activation/up-regulation of Pin1, while the inverse correlation between Pin1 activity and phosphorylated tau in NCI group implies that decreased Pin1 may play a role in the initial accumulation of phosphorylated tau in AD pathogenesis. Show more

Keywords: Alzheimer's disease, Pin1, tau, cognitive, dementia, MCI, AD

DOI: 10.3233/JAD-2007-11105

Citation: Journal of Alzheimer's Disease, vol. 11, no. 1, pp. 13-23, 2007

Authors: Wang, Deng-Shun | Uchikado, Hirotake | Bennett, David A. | Schneider, Julie A. | Mufson, Elliott J. | Wu, Joanne | Dickson, Dennis W.

Article Type: Research Article

Abstract: Background:: Protein cross-linking and aggregation are important molecular processes in Alzheimer’s disease (AD), and tissue transglutaminase (tTG) catalyzes protein cross-linking. Objectives:: To measure tTG, tTG enzyme activity and isopeptide, which is the product of tTG, in brain and to relate them to cognitive scores. Methods:: tTG and isopeptide levels were measured in frontal gray matter of 10 normal (NCI), 10 mild cognitive impairment (MCI) and 9 AD brains from the Religious Orders Study. tTG enzymatic activity was measured with a fluorescence assay. Results:: tTG protein and enzyme activity were highest in AD, but not significantly greater than MCI or NCI. …In contrast, isopeptide immunoreactivity in formic acid extracts was significantly greater in AD than NCI and MCI. The level of insoluble formic acid extractable isopeptide correlated with several measures of cognitive function, including word generation and perceptual speed. Multiple linear regression analyses indicated that insoluble isopeptide immunoreactivity could be accounted for by a combination of factors in the formic acid extract, including Aβ, ubiquitin and tau. Conclusions:: Accumulation of insoluble proteins with isopeptide bonds correlates with cognitive impairment. The relationship of isopeptide to other proteins that are also enriched in formic acid extracts suggests that several substrates of tTG may play a role in the pathogenesis of AD. Show more

Keywords: Amyloid, isopeptide, mental status, neuropsychology, tau, transglutaminase, ubiquitin

DOI: 10.3233/JAD-2008-13106

Citation: Journal of Alzheimer's Disease, vol. 13, no. 1, pp. 53-66, 2008