Your search for: 'author:("Wang, Zhan-You")' has returned 5 results. (0.016s) Save search

Authors: Wang, Tao | Wang, Chun-Yan | Shan, Zhong-Yan | Teng, Wei-Ping | Wang, Zhan-You

Article Type: Research Article

Abstract: Metal dyshomeostasis in the brain helps promote amyloid-β (Aβ) deposition in Alzheimer's disease (AD). Therefore, targeting the interactions between metal and Aβ is a potential therapeutic approach for AD. The metal chelator, clioquinol (CQ), is thought to reduce Aβ deposits in the AD transgenic mouse brain, and attenuate the clinical symptoms of AD patients. However, whether oral administration of CQ reduces zinc accumulation in Aβ plaques and inhibits the amyloidogenic pathway have not been properly established in AD transgenic mice. By means of autometallographic analysis, we show for the first time that both the number and size of the zinc-containing …plaques were significantly reduced in the brain of amyloid-β protein precursor (AβPP)/presenilin 1 (PS1) double transgenic mice treated with CQ (30 mg/kg/day) orally for 2 months. This was accompanied by a reduction in Aβ burden in the CQ-treated mouse brain. Furthermore, CQ treatment markedly reduced the expression levels of AβPP protein, the β-site of AβPP cleaving enzyme 1 (BACE1), PS1, and the secreted β-secretase-derived fragments of AβPP (sAβPPβ). The present data indicate that CQ is able to reduce zinc accumulation in the neuritic plaques and inhibit amyloidogenic AβPP processing in the AβPP/PS1 mouse brain. Show more

Keywords: AβPP/PS1 transgenic mouse, Alzheimer's disease, amyloid-β, amyloidogenic pathway, clioquinol, zinc

DOI: 10.3233/JAD-2011-111874

Citation: Journal of Alzheimer's Disease, vol. 29, no. 3, pp. 549-559, 2012

Authors: Li, Yin | Li, Ze-Xu | Jin, Tan | Wang, Zhan-You | Zhao, Pu

Article Type: Research Article

Abstract: Hyaluronic acid (HA) is the backbone of the extracellular matrix (ECM) and provides biochemical and physical support to aggrecan-based perineuronal nets (PNNs), which are associated with the selective vulnerability of neurons in Alzheimer’s disease (AD). Here, we showed that HA synthases (HASs), including Has1, Has2, and Has3, were widely expressed in murine central nervous system. All types of HASs were localized to cell bodies of neurons; only Has1 existed in the membranes of neural axons. By using TauP301S transgenic (Tg) mouse model, we found that the axonal-localization of Has1 was abolished in TauP301S overexpressed mouse brain, and the redistribution of …Has1 was also observed in human AD brains, suggesting that the localization of Has1 is dependent on intact microtubules which are regulated partially by the phosphorylation and dephosphorylation cycles of tau proteins. Furthermore, Has1 was reduced and Has3 was increased in TauP301S Tg mouse brain, resulting in the upregulation of shorter-chain HA in the ECM. These findings suggest that by abolishing the axonal-localization of Has1 and promoting the expression of Has3 and the synthesis of shorter-chain HA, the tau pathology breaks the balance of ECM components, promotes the reorganization of the ECM, and inhibits the formation of PNNs in the hippocampus, and then regulates neuronal plasticity during the progression of AD. Show more

Keywords: Alzheimer’s disease, extracellular matrix, hyaluronan synthase, hyaluronic acid, tau pathology

DOI: 10.3233/JAD-160804

Citation: Journal of Alzheimer's Disease, vol. 57, no. 2, pp. 395-409, 2017

Authors: Zheng, Wei | Wang, Tao | Yu, Dan | Feng, Wan-Yu | Nie, Ying-Xue | Stoltenberg, Meredin | Danscher, Gorm | Wang, Zhan-You

Article Type: Research Article

Abstract: The presence of senile plaques containing abundant amyloid-β (Aβ) peptide is one of the major pathological hallmarks of Alzheimer's disease (AD). Recent studies support the notion that overexpression of zinc transporters (ZnT) is involved in zinc metabolic disturbances and Aβ aggregation in AD brains. Here we present data showing an elevated expression of zinc transporter 3 (ZnT3) protein, revealed by immunoblotting assay, in the cerebellum of the amyloid-β protein precursor (AβPP)/presenilin 1 (PS1) transgenic mouse. Confocal microscopic and autometallographic results showed that ZnT3 immunofluorescence and zinc ions were predominantly located in the amyloid plaques. ZnT3 protein was abundantly distributed throughout …the plaques, whereas zinc ions were mainly located in the peripheral parts of rosette-shaped plaques with a lightly stained center. Collectively, our results suggest that ZnT3 protein is involved in the Aβ aggregation in the cerebellum of the AβPP/PS1 mouse. Show more

Keywords: Alzheimer's disease, amyloid-β peptide, cerebellum, ionic zinc, SLC30A3

DOI: 10.3233/JAD-2010-1363

Citation: Journal of Alzheimer's Disease, vol. 20, no. 1, pp. 323-331, 2010

Authors: Gao, Hui-ling | Li, Cheng | Nabeka, Hiroaki | Shimokawa, Tetsuya | Wang, Zhan-You | Cao, Ya-ming | Matsuda, Seiji

Article Type: Research Article

Abstract: The pathological hallmarks of Alzheimer’s disease (AD) include amyloid-β (Aβ) accumulation, neurofibrillary tangle formation, synaptic dysfunction, and neuronal loss. The present study was performed to investigate the protective effects and mechanism of action of a prosaposin-derived 18-mer peptide (PS18: LSELIINNATEELLIKGL) on mice hippocampal progenitor cell proliferation, neurogenesis, and memory tasks after intracerebroventricular injection of Aβ1–42 peptide. Seven days after Aβ1–42 injection, significant proliferation of hippocampal progenitor cells and memory impairment were evident. Two weeks after Aβ1–42 peptide injection, elevated numbers of surviving 5-bromo-2-deoxyuridine cells and newly formed neurons were detected. Treatment with PS18 attenuated these effects evoked by Aβ1–42 . …Our data indicate that treatment with PS18 partially attenuated the increase in hippocampal neurogenesis caused by Aβ1–42 -induced neuroinflammation and prevented memory deficits associated with increased numbers of activated glial cells. We observed an increase in ADAM10 and decreases in BACE1, PS1/2, and AβPP protein levels, suggesting that PS18 enhances the nonamyloidogenic AβPP cleavage pathway. Importantly, our results further showed that PS18 activated the PI3K/Akt pathway, phosphorylated GSK-3α/β, and, as a consequence, exerted a neuroprotective effect. In addition, PS18 showed a protective effect against Aβ1–42 -induced neurotoxicity via suppression of the caspase pathway; upregulation of Bcl-2; downregulation of BAX, attenuating mitochondrial damage; and inhibition of caspase-3. These findings suggest that PS18 may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative diseases, such as AD. Show more

Keywords: Aβ1–42 peptide, Akt/GSK-3α/β, Alzheimer’s disease, apoptosis, neurogenesis, prosaposin

DOI: 10.3233/JAD-160093

Citation: Journal of Alzheimer's Disease, vol. 53, no. 3, pp. 1173-1192, 2016

Authors: Tian, Li | Zhang, Ke | Tian, Zhi-Ying | Wang, Tao | Shang, De-Shu | Li, Bo | Liu, Dong-Xin | Fang, Wen-Gang | Wang, Zhan-You | Chen, Yu-Hua

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative dementia characterized by pathological senile plaques composed of amyloid-β (Aβ) in the cerebral cortex and hippocampus. Bone marrow-derived monocytes of patients with AD migrate across the blood-brain barrier into the brain, but are defective at clearing Aβ in the neuritic plaques. However, the underlying mechanisms remain unclear. Here, in patients with AD, we found that cathepsin D, a major lysosomal aspartic protease, was underexpressed in monocytes, resulting in the defective degradation of Aβ by monocytes/macrophages. Further, downregulation of cathepsin D in THP-1 cells significantly reduced the clearance of amyloid plaques in the brain …sections of AβPP/PS1 mice. The clearance ability was recovered by the overexpression of cathepsin D in AD monocytes. These results suggest that decreased expression of cathepsin D in the peripheral monocytes is a potential signature of AD, and that this decreased expression is involved in Aβ degradation and AD pathogenesis. Show more

Keywords: Alzheimer's disease, amyloid-β, cathepsin D, monocyte

DOI: 10.3233/JAD-132192

Citation: Journal of Alzheimer's Disease, vol. 42, no. 2, pp. 511-520, 2014