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Glucagon-like peptide-1 protects hippocampal neurons against advanced glycation end product-induced tau hyperphosphorylation.

Abstract

We have previously demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonist ameliorated neurodegenerative changes in rat models of diabetes-related Alzheimer's disease (AD), and protected neurons from glucose toxicity in vitro. Herein, we investigated the effects of GLP-1 receptor mediates on cell toxicity and tau hyperphosphorylation induced by advanced glycation end products (AGEs), which are associated with glucose toxicity, and the molecular mechanism in PC12 cells and the primary hippocampal neurons. Our study demonstrated that the similar protection effects of GLP-1 existed in PC12 cells treated with glucose-bovine serum albumin (BSA) in hyperglycemic conditions or with glycoaldehyde-BSA alone. Additionally, glucose-BSA alone did not induce significant cytotoxicity in PC12 cells, but resulted in tau hyperphosphorylation in primary hippocampal neurons in 24h. And we found that GLP-1 could reduce cell tau phosphorylation induced by high glucose or glucose-BSA. Furthermore, our data in the present study suggested that GLP-1 regulated tau phosphorylation induced by AGEs through a signaling pathway involving glycogen synthase kinase 3β (GSK-3β), similarly to the GSK-3β inhibitor, lithium chloride. Our findings suggest that GLP-1 can protect neurons from diabetes-associated AGE insults in vitro, and provide new evidence for a potential therapeutic value of GLP-1 receptor agonist in the treatment of AD especially diabetes-related AD.

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  • Publisher Full Text
  • Authors+Show Affiliations

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    State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.

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    State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.

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    State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China.

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    Medical School, Southeast University, Nanjing 210009, PR China.

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    School of Pharmacy, Anhui College of Traditional Chinese Medicine, Hefei 230038, PR China.

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    State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: wbyao@cpu.edu.cn.

    State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: xiangdong_gao@qq.com.

    Source

    Neuroscience 256: 2014 Jan 03 pg 137-46

    MeSH

    Androstadienes
    Animals
    Cell Survival
    Cells, Cultured
    Dose-Response Relationship, Drug
    Embryo, Mammalian
    Enzyme Inhibitors
    Glucagon-Like Peptide 1
    Glucose
    Glycation End Products, Advanced
    Glycogen Synthase Kinase 3
    Glycogen Synthase Kinase 3 beta
    Hippocampus
    Neurons
    Neuroprotective Agents
    Phosphorylation
    Rats
    Rats, Wistar
    Serine
    Serum Albumin, Bovine
    Wortmannin
    tau Proteins

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24183963

    Citation

    Chen, S, et al. "Glucagon-like Peptide-1 Protects Hippocampal Neurons Against Advanced Glycation End Product-induced Tau Hyperphosphorylation." Neuroscience, vol. 256, 2014, pp. 137-46.
    Chen S, An FM, Yin L, et al. Glucagon-like peptide-1 protects hippocampal neurons against advanced glycation end product-induced tau hyperphosphorylation. Neuroscience. 2014;256:137-46.
    Chen, S., An, F. M., Yin, L., Liu, A. R., Yin, D. K., Yao, W. B., & Gao, X. D. (2014). Glucagon-like peptide-1 protects hippocampal neurons against advanced glycation end product-induced tau hyperphosphorylation. Neuroscience, 256, pp. 137-46. doi:10.1016/j.neuroscience.2013.10.038.
    Chen S, et al. Glucagon-like Peptide-1 Protects Hippocampal Neurons Against Advanced Glycation End Product-induced Tau Hyperphosphorylation. Neuroscience. 2014 Jan 3;256:137-46. PubMed PMID: 24183963.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Glucagon-like peptide-1 protects hippocampal neurons against advanced glycation end product-induced tau hyperphosphorylation. AU - Chen,S, AU - An,F-M, AU - Yin,L, AU - Liu,A-R, AU - Yin,D-K, AU - Yao,W-B, AU - Gao,X-D, Y1 - 2013/10/30/ PY - 2013/08/17/received PY - 2013/10/13/revised PY - 2013/10/20/accepted PY - 2013/11/5/entrez PY - 2013/11/5/pubmed PY - 2014/8/29/medline KW - 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide KW - AD KW - AGEs KW - APP KW - Alzheimer’s disease KW - Aβ KW - BSA KW - DM KW - DMSO KW - DPP-IV KW - Ex-4 KW - FBS KW - GLP-1 KW - GLP-1R KW - GLP-1RA KW - GSK-3β KW - HG KW - ICV-STZ KW - MTT KW - NFTs KW - PBS KW - PHF KW - PI3-K KW - RAGE KW - advanced glycation end products KW - amyloid precursor protein KW - amyloid β-peptide KW - bovine serum albumin KW - diabetes mellitus KW - diabetes-related Alzheimer’s disease KW - dimethyl sulfoxide KW - dipeptidyl peptidase IV KW - exendin-4 KW - fetal bovine serum KW - glucagon-like peptide-1 KW - glucagon-like peptide-1 receptor KW - glucagon-like peptide-1 receptor agonist KW - glycogen synthase kinase 3β KW - glycogen synthase kinase-3β KW - high glucose KW - intracerebroventricular-streptozotocin KW - neurofibrillary tangles KW - paired helical filament KW - phosphate buffer saline KW - phosphatidyl inositol 3 kinase KW - receptor for advanced glycation end products KW - tau SP - 137 EP - 46 JF - Neuroscience JO - Neuroscience VL - 256 N2 - We have previously demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonist ameliorated neurodegenerative changes in rat models of diabetes-related Alzheimer's disease (AD), and protected neurons from glucose toxicity in vitro. Herein, we investigated the effects of GLP-1 receptor mediates on cell toxicity and tau hyperphosphorylation induced by advanced glycation end products (AGEs), which are associated with glucose toxicity, and the molecular mechanism in PC12 cells and the primary hippocampal neurons. Our study demonstrated that the similar protection effects of GLP-1 existed in PC12 cells treated with glucose-bovine serum albumin (BSA) in hyperglycemic conditions or with glycoaldehyde-BSA alone. Additionally, glucose-BSA alone did not induce significant cytotoxicity in PC12 cells, but resulted in tau hyperphosphorylation in primary hippocampal neurons in 24h. And we found that GLP-1 could reduce cell tau phosphorylation induced by high glucose or glucose-BSA. Furthermore, our data in the present study suggested that GLP-1 regulated tau phosphorylation induced by AGEs through a signaling pathway involving glycogen synthase kinase 3β (GSK-3β), similarly to the GSK-3β inhibitor, lithium chloride. Our findings suggest that GLP-1 can protect neurons from diabetes-associated AGE insults in vitro, and provide new evidence for a potential therapeutic value of GLP-1 receptor agonist in the treatment of AD especially diabetes-related AD. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/24183963/Glucagon_like_peptide_1_protects_hippocampal_neurons_against_advanced_glycation_end_product_induced_tau_hyperphosphorylation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(13)00891-9 DB - PRIME DP - Unbound Medicine ER -