Glucagon-like peptide-1 (GLP-1) diminishes neuronal degeneration and death caused by NGF deprivation by suppressing Bim induction.
Glucagon-like peptide-1 (GLP-1) is a glucoincretin hormone most intensively studied for its actions on insulin secreting beta-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.
Biswas
Subhas C
SC
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. scb34@columbia.edu
Buteau
Jean
J
Greene
Lloyd A
LA
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D016923:Cell Death / Q000502:physiology*; D002478:Cells, Cultured; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism*; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D052216:Glucagon-Like Peptide 1; D020932:Nerve Growth Factor