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

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2008 Mar 21

PMID 18351462

Citations 20

Authors

Subhas C Biswas

Jean Buteau

Lloyd A Greene

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Catalpol alleviates amyloid- generation and neuronal oxidative stress injury via activating the Keap1-Nrf2/ARE signaling pathway in the immortalized lymphocytes from patients with late-onset Alzheimer's disease and SKNMC cells co-culture model.

Xiang C, Lu Y, Hao R, Wei Y, Hu Y, Yu G Iran J Basic Med Sci. 2024; 27(12):1547-1557.

PMID: 39539442 PMC: 11556766. DOI: 10.22038/ijbms.2024.78543.16982.

GLP-1/GIP Agonist as an Intriguing and Ultimate Remedy for Combating Alzheimer's Disease through its Supporting DPP4 Inhibitors: A Review.

Abubakar M, Nama L, Ansari M, Ansari M, Bhardwaj S, Daksh R Curr Top Med Chem. 2024; 24(19):1635-1664.

PMID: 38803170 DOI: 10.2174/0115680266293416240515075450.

Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats.

Guo X, Lei M, Zhao J, Wu M, Ren Z, Yang X Front Pharmacol. 2023; 14:1146960.

PMID: 37701028 PMC: 10493299. DOI: 10.3389/fphar.2023.1146960.

The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer's disease.

Du H, Meng X, Yao Y, Xu J Front Endocrinol (Lausanne). 2022; 13:1033479.

PMID: 36465634 PMC: 9714676. DOI: 10.3389/fendo.2022.1033479.

Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats.

Kim S, Park T, Jin H Diabetes Metab J. 2020; 44(6):842-853.

PMID: 32602278 PMC: 7801759. DOI: 10.4093/dmj.2019.0190.

References

Trumper K, Trumper A, Trusheim H, Arnold R, Goke B, Horsch D . Integrative mitogenic role of protein kinase B/Akt in beta-cells. Ann N Y Acad Sci. 2001; 921:242-50. DOI: 10.1111/j.1749-6632.2000.tb06972.x. View

Perry T, Lahiri D, Chen D, Zhou J, Shaw K, Egan J . A novel neurotrophic property of glucagon-like peptide 1: a promoter of nerve growth factor-mediated differentiation in PC12 cells. J Pharmacol Exp Ther. 2002; 300(3):958-66. DOI: 10.1124/jpet.300.3.958. View

Ham J, Eilers A, Whitfield J, Neame S, Shah B . c-Jun and the transcriptional control of neuronal apoptosis. Biochem Pharmacol. 2000; 60(8):1015-21. DOI: 10.1016/s0006-2952(00)00372-5. View

Goke R, Larsen P, Mikkelsen J, Sheikh S . Identification of specific binding sites for glucagon-like peptide-1 on the posterior lobe of the rat pituitary. Neuroendocrinology. 1995; 62(2):130-4. DOI: 10.1159/000126997. View

Park D, Morris E, Stefanis L, Troy C, Shelanski M, Geller H . Multiple pathways of neuronal death induced by DNA-damaging agents, NGF deprivation, and oxidative stress. J Neurosci. 1998; 18(3):830-40. PMC: 6792759. View

Friedman W, Greene L . Neurotrophin signaling via Trks and p75. Exp Cell Res. 1999; 253(1):131-42. DOI: 10.1006/excr.1999.4705. View

Buteau J, El-Assaad W, Rhodes C, Rosenberg L, Joly E, Prentki M . Glucagon-like peptide-1 prevents beta cell glucolipotoxicity. Diabetologia. 2004; 47(5):806-15. DOI: 10.1007/s00125-004-1379-6. View

Biswas S, Greene L . Nerve growth factor (NGF) down-regulates the Bcl-2 homology 3 (BH3) domain-only protein Bim and suppresses its proapoptotic activity by phosphorylation. J Biol Chem. 2002; 277(51):49511-6. DOI: 10.1074/jbc.M208086200. View

Merchenthaler I, Lane M, Shughrue P . Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system. J Comp Neurol. 1999; 403(2):261-80. DOI: 10.1002/(sici)1096-9861(19990111)403:2<261::aid-cne8>3.0.co;2-5. View

10.

Biswas S, Shi Y, Vonsattel J, Leung C, Troy C, Greene L . Bim is elevated in Alzheimer's disease neurons and is required for beta-amyloid-induced neuronal apoptosis. J Neurosci. 2007; 27(4):893-900. PMC: 6672914. DOI: 10.1523/JNEUROSCI.3524-06.2007. View

11.

Greig N, Mattson M, Perry T, Chan S, Giordano T, Sambamurti K . New therapeutic strategies and drug candidates for neurodegenerative diseases: p53 and TNF-alpha inhibitors, and GLP-1 receptor agonists. Ann N Y Acad Sci. 2005; 1035:290-315. DOI: 10.1196/annals.1332.018. View

12.

Spires T, Hyman B . Neuronal structure is altered by amyloid plaques. Rev Neurosci. 2004; 15(4):267-78. DOI: 10.1515/revneuro.2004.15.4.267. View

13.

Willis S, Adams J . Life in the balance: how BH3-only proteins induce apoptosis. Curr Opin Cell Biol. 2005; 17(6):617-25. PMC: 2930980. DOI: 10.1016/j.ceb.2005.10.001. View

14.

Biswas S, Liu D, Greene L . Bim is a direct target of a neuronal E2F-dependent apoptotic pathway. J Neurosci. 2005; 25(37):8349-58. PMC: 6725681. DOI: 10.1523/JNEUROSCI.1570-05.2005. View

15.

Greene L, Tischler A . Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A. 1976; 73(7):2424-8. PMC: 430592. DOI: 10.1073/pnas.73.7.2424. View

16.

Sofroniew M, Howe C, Mobley W . Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci. 2001; 24:1217-81. DOI: 10.1146/annurev.neuro.24.1.1217. View

17.

Whitfield J, Neame S, Paquet L, Bernard O, Ham J . Dominant-negative c-Jun promotes neuronal survival by reducing BIM expression and inhibiting mitochondrial cytochrome c release. Neuron. 2001; 29(3):629-43. DOI: 10.1016/s0896-6273(01)00239-2. View

18.

Williams B, Eriksdotter-Jonhagen M, Granholm A . Nerve growth factor in treatment and pathogenesis of Alzheimer's disease. Prog Neurobiol. 2006; 80(3):114-28. DOI: 10.1016/j.pneurobio.2006.09.001. View

19.

Rukenstein A, Rydel R, Greene L . Multiple agents rescue PC12 cells from serum-free cell death by translation- and transcription-independent mechanisms. J Neurosci. 1991; 11(8):2552-63. PMC: 6575525. View

20.

Gilley J, Coffer P, Ham J . FOXO transcription factors directly activate bim gene expression and promote apoptosis in sympathetic neurons. J Cell Biol. 2003; 162(4):613-22. PMC: 2173804. DOI: 10.1083/jcb.200303026. View