跳至主要内容

DA5-CH, a novel GLP-1/GIP dual agonist, effectively ameliorates the cognitive impairments and pathology in the APP/PS1 mouse model of Alzheimer's disease

文献作者：YueCao, Christian H?lscher, Meng-Ming Hu, Ting Wang, Fang Zhao, Yu Bai, Jun Zhang, Mei-Na Wu, Jin-Shun Qi   《European Journal of Pharmacology》

ABSTRACTS
Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there is no cure. The early primary symptom of AD is the decline of memory ability, which gradually develops into complete dementia. Type 2 diabetes mellitus (T2DM) is an important risk factor of AD; and mimetics of the incretin hormone GLP-1 developed to treat diabetes are being tested as a novel therapeutic strategy for AD. In the present study, we reported for the first time the neuroprotective effects of a novel GLP-1/GIP dual agonist DA5-CH that activates the incretin hormone GLP-1 and GIP receptors in the APP/PS1 transgenic AD mouse model. We found that: (1) DA5-CH administration effectively improved working-memory and long-term spatial memory of 9-month-old AD mice in Y-maze and Morris water maze tests; (2) DA5-CH also reduced hippocampal amyloid senile plaques and phosphorylated tau protein levels; (3) DA5-CH basically reversed the deficits in hippocampal late-phase long-term potentiation; (4) DA5-CH up-regulated the levels of p-PI3K and p-AKT growth factor kinases and prevented excessive activation of p-GSK3β in the hippocampus of APP/PS1 mice. Therefore, the neuroprotection of DA5-CH in alleviating cognitive impairments and pathological damages might be associated with the improvement of hippocampal synaptic plasticity and activation of the PI3K/AKT signaling pathway. We propose that DA5-CH may be beneficial for the treatment of AD patients, especially those with T2DM or hyperglycemia.
KEY WORDS
GLP-1/GIP dual agonist; APP/PS1 AD mice; Working memory; Long term memory; L-LTP; Amyloid-β protein; Phosphorylated tau protein; PI3K/AKT/GSK3β
SCREENSHOT

RELATED PRODUCTS
The dual agonist DA5-CH was gotten from Chinapeptides Ltd (Shanghai, China).
CHAINING
https://www.sciencedirect.com/science/article/pii/S001429991830178X
标签：

评论

发表评论

此博客中的热门博文

The therapeutic effect of anti-CD52 treatment in murine experimental autoimmune encephalomyelitis is associated with altered IL-33 and ST2 expression levels

文献作者：Mark Barbour, Rachel Wood, Shehla U.Hridi, Chelsey Wilson, Grant McKay, Trevor J.Bushell, Hui-Rong Jiang   《Journal of Neuroimmunology》 ABSTRACTS Experimental autoimmune encephalomyelitis  (EAE) mice were administered with murine anti-CD52  antibody  to investigate its therapeutic effect and whether the treatment modulates IL-33 and ST2 expression. EAE severity and  central nervous system  (CNS) inflammation were reduced following the treatment, which was accompanied by peripheral  T and B lymphocyte  depletion and reduced production of various  cytokines  including IL-33, while sST2 was increased. In spinal cords of EAE mice, while the number of IL-33 +  cells remained unchanged, the extracellular level of IL-33 protein was significantly reduced in anti-CD52 antibody treated mice compared with controls. Furthermore the number of ST2 +  cells in the spinal cord of treated EAE mice was  downregulated ...
发表评论
阅读全文

Mutational analysis of the extracellular disulphide bridges of the atypical chemokine receptor ACKR3/CXCR7 uncovers multiple binding and activation modes for its chemokine and endogenous non-chemokine agonists

Author：Martyna Szpakowska, Max Meyrath, Nathan Reynders,  Manuel Counson, Julien Hanson, Jan Steyaert, Andy Chevigné     《Biochemical Pharmacology》 ABSTRACTS The atypical chemokine receptor ACKR3/CXCR7 plays crucial roles in numerous physiological processes but also in viral infection and cancer. ACKR3 shows strong propensity for activation and, unlike classical chemokine receptors, can respond to chemokines from both the CXC and CC families as well as to the endogenous peptides BAM22 and adrenomedullin. Moreover, despite belonging to the G protein coupled receptor family, its function appears to be mainly dependent on β-arrestin. ACKR3 has also been shown to continuously cycle between the plasma membrane and the endosomal compartments, suggesting a possible role as a scavenging receptor. So far, the molecular basis accounting for these atypical binding and signalling properties remains elusive. Noteworthy, ACKR3 extracellular domains bear three  di...
发表评论
阅读全文

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...
1 条评论
阅读全文