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A novel GLP1/GIP/Gcg triagonist reduces cognitive deficits and pathology in the 3xTg mouse model of Alzheimer's disease

文献作者:Tian Li , JuanJuan Jiao, Christian Hölscher, MeiNa Wu, Jun Zhang, JiaQing Tong, XueFan Dong, XueSong Qu, Yue Cao, HongYan Cai, Qiang Su, JinShun Qi   《Hippocampus》


ABSTRACTS
Type 2 diabetes mellitus (T2DM) is an important risk factor for Alzheimer's disease (AD). Glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) have been identified to be effective in T2DM treatment and neuroprotection. In this study, we further explored the effects of a novel unimolecular GLP‐1/GIP/Gcg triagonist on the cognitive behavior and cerebral pathology in the 7‐month‐old triple transgenic mouse model of AD (3xTg‐AD), and investigated its possible electrophysiological and molecular mechanisms. After chronic administration of the GLP‐1/GIP/Gcg triagonist (10 nmol/kg bodyweight, once daily, i.p.) for 30 days, open field, Y maze and Morris water maze tests were performed, followed by in vivoelectrophysiological recording, immunofluorescence and Western blotting experiments. We found that the chronic treatment with the triagonist could improve long‐term spatial memory of 3xTg‐AD mice in Morris water maze, as well as the working memory in Y maze task. The triagonist also alleviated the suppression of long‐term potentiation (LTP) in the CA1 region of hippocampus. In addition, the triagonist significantly reduced hippocampal pathological damages, including amyloid‐β (Aβ) and phosphorylated tau aggregates, and upregulated the expression levels of S133p‐CREB, T286p‐CAMKII and S9p‐GSK3β in the hippocampus of the 3xTg‐AD mice. These results demonstrate for the first time that the novel GLP‐1/GIP/Gcg triagonist is efficacious in ameliorating cognitive deficits and pathological damages of 3xTg‐AD mice, suggesting that the triagonist might be potentially beneficial in the treatment of AD.
SCREENSHOT

RELATED PRODUCTS
The triple agonists (purity: 95%); GLP1/GIP/Gcg triagonist
CHAINING
https://onlinelibrary.wiley.com/doi/abs/10.1002/hipo.22837

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CAS:85466-18-8|Thymopoietin II (32-35)|RKDV

Contact: Liven Qian(钱叶华)-Custom Peptide Mobile: 13761298676(微信) Email:cps037@chinapeptides.net QQ:2880526724 ChinaPeptides Co., Ltd./强耀生物科技有限公司 Name Thymopoietin II (32-35) Code [85466-18-8] The alias Thymopoietin II (32-35) Sequence (single letter abbreviation) RKDV Sequence (three-letter abbreviation) H-Arg-Lys-Asp-Val-OH (trifluoroacetate salt) A basic description TP-4 and TP-3; shortest active thymopoietin II fragments described that exhibit potent immunoregulatory properties in vitro and in vivo. solubility The molecular weight 516.6 Chemical formula C21H40N8O7 The purity 80%,90%,95%,98%,99% Weight 1mg,5mg,10mg,50mg,100mg,1g Storage conditions Store at -20°C. Keep tightly closed. Store in a cool dry place. Number of Residues: 4 1-Letter Code: RKDV 3-Letter Code: Arg-Lys-Asp-Val Molecular weight (Mr): 516.6 g/mol Isoelectric point: 10.1 Net charge at pH 7.0: 1.0 Average hydrophilicity: 1.9 Ratio of hydrophilic residues / total number of residues...