کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8517247 | 1556586 | 2018 | 40 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
GLP-1 receptor agonists downregulate aberrant GnT-III expression in Alzheimer's disease models through the Akt/GSK-3β/β-catenin signaling
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
Alterations of glycoprotein glycans contribute to a wide variety of diseases. Bisecting N-acetylglucosamine (GlcNAc) levels increased in the cerebrospinal fluid of most Alzheimer's disease (AD) patients, and the mRNA levels of N-acetylglucosaminyltransferase III (GnT-III), a glycosyltransferase responsible for synthesizing a bisecting GlcNAc residue, were found highly expressed in the brains of AD patients. In our previous studies, glucagon-like peptide-1 (GLP-1) and its mimetics showed neuroprotective effects. Here, we confirmed that four weeks' treatment of exendin-4 could rescue memory deficits and neuropathological changes in APP/PS1 mice. We further explored the underlying mechanism and especially the role of GnT-III in it. We demonstrated for the first time that the levels of GnT-III and bisecting GlcNAc were increased in APP/PS1 mice and Aβ25-35-treated PC12 cells, and GLP-1 receptor agonists (GLP-1RA) could downregulate aberrant neuronal expression of GnT-III and bisecting GlcNAc. We also found that GLP-1RA recovered the phosphorylation levels of Akt (Ser473) and GSK-3β (Ser9) and the levels of β-catenin in mice and cell models. Furthermore, the results indicated that inhibitor LY294002 attenuated these effects of GLP-1RA in PC12 cells, and β-catenin siRNA abolished the effect of GLP-1RA on GnT-III. In summary, our results suggest that GnT-III plays an important role in AD and GLP-1RA could downregulate aberrant GnT-III expression through the Akt/GSK-3β/β-catenin signaling pathway in neurons.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 131, 15 March 2018, Pages 190-199
Journal: Neuropharmacology - Volume 131, 15 March 2018, Pages 190-199
نویسندگان
Ying Wang, Song Chen, Zheng Xu, Suting Chen, Wenbing Yao, Xiangdong Gao,