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Glucagon-like Peptide-1 (GLP-1) Diminishes Neuronal Degeneration and Death Caused by NGF Deprivation by Suppressing Bim Induction

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Abstract

Glucagon-like peptide-1 (GLP-1) is a glucoincretin hormone most intensively studied for its actions on insulin secreting β-cells. GLP-1 and its receptor are also found in brain and accumulating evidence indicates that GLP-1 has neuroprotective actions. Here, we investigated whether GLP-1 protects neuronal cells from death evoked by nerve growth factor (NGF) withdrawal. Compromised trophic factor signaling may underlie neurodegenerative diseases ranging from Alzheimer disease to diabetic neuropathies. We report that GLP-1 provides sustained protection of cultured neuronal PC12 cells and sympathetic neurons from degeneration and death caused by NGF deprivation. Past work shows that NGF deprivation induces the pro-apoptotic protein Bim which contributes to neuron death. Here, we find that GLP-1 suppresses Bim induction promoted by NGF deprivation. Thus, GLP-1 may protect neurons, at least in part, by suppressing Bim induction. Our findings support the idea that drugs that mimic or elevate GLP-1 represent potential therapeutics for neurodegenerative diseases.

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Acknowledgements

We thank Dr. Yijie Shi for excellent technical assistance. We also acknowledge the aid of Dr. Dominic Accili. Supported in part by grants from the NIH-NINDS and Parkinson’s Disease Foundation.

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Authors and Affiliations

  1. Department of Pathology, Center for Neurobiology and Behavior and Taub Center for Alzheimer’s Disease Research, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA

    Subhas C. Biswas & Lloyd A. Greene

  2. Department of Anatomy and Physiology, Universite Laval and Centre de Recherche de l’Hopital, Laval 2725 Ch. Ste-Foy, Local Y-3120, Quebec, QC, Canada, G1V 4G5

    Jean Buteau

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  1. Subhas C. Biswas
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  2. Jean Buteau
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  3. Lloyd A. Greene
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Correspondence to Subhas C. Biswas.

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Biswas, S.C., Buteau, J. & Greene, L.A. Glucagon-like Peptide-1 (GLP-1) Diminishes Neuronal Degeneration and Death Caused by NGF Deprivation by Suppressing Bim Induction. Neurochem Res 33, 1845–1851 (2008). https://doi.org/10.1007/s11064-008-9646-4

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  • DOI: https://doi.org/10.1007/s11064-008-9646-4

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