Skip to main content
Log in

Potential Role of Glucagon-Like Peptide-1 (GLP-1) in Neuroprotection

  • Review Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

The current understanding of neurodegenerative processes in sporadic diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) or multiple sclerosis is very limited. Several risk factors have been identified that may shed light on the underlying mechanisms that initiate the neurodegeneration. Type 2 diabetes mellitus has been identified as a risk factor for AD and PD. In AD patients, desensitization of insulin receptors in the brain has been shown, even in non-diabetic patients. Insulin acts as a growth factor in the brain and supports neuronal repair, dendritic sprouting and synaptogenesis, and protection from oxidative stress. Importantly, several drugs have been developed to treat type 2 diabetes that re-sensitize insulin receptors and may be of use to prevent neurodegenerative processes. Glucagon-like peptide-1 (GLP-1) is a hormone that facilitates insulin release under high blood sugar conditions. Interestingly, GLP-1 also has very similar growth factor-like properties to insulin, and has been shown to reduce a range of degenerative processes. In pre-clinical studies, GLP-1 and longer-lasting protease-resistant analogues cross the blood-brain barrier, protect memory formation (AD) or motor activity (PD), protect synapses and synaptic functions, enhance neurogenesis, reduce apoptosis, protect neurons from oxidative stress, and reduce plaque formation and the chronic inflammation response in the brains of mouse models of AD, PD, amyotrophic lateral sclerosis, stroke and other degenerative diseases. GLP-1 signalling does not affect blood sugar levels in non-diabetic people and therapies that affect GLP-1 signalling have a good safety profile as shown by the chronic application of drugs currently on the market (liraglutide, Victoza®; NovoNordisk, Copenhagen, Denmark, and exendin-4, Byetta®; Amylin, San Diego, CA, USA). Based on the extensive evidence, several clinical trials are currently underway, testing liraglutide and exendin-4 in AD and PD patients. Therefore, GLP-1 analogues show great promise as a novel treatment for AD or other neurodegenerative conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Hölscher C. Possible causes of Alzheimer’s disease: amyloid fragments, free radicals, and calcium homeostasis. Neurobiol Dis 1998; 5(3): 129–41

    Article  PubMed  Google Scholar 

  2. Bossy WE, Schwarzenbacher R, Lipton SA. Molecular pathways to neurodegeneration. Nat Med 2004; 10 Suppl.: S2–9

    Article  Google Scholar 

  3. Harkavyi A, Whitton PS. Glucagon-like peptide 1 receptor stimulation as a means of neuroprotection. Br J Pharmacol 2010; 159(3): 495–501

    Article  PubMed  CAS  Google Scholar 

  4. Aharoni R. Immunomodulatory drug treatment in multiple sclerosis. Exp Rev Neurother 2010; 10(9): 1423–36

    Article  CAS  Google Scholar 

  5. Chen SY, Chen TF, Lai LC, et al. Sequence variants of interleukin 6 (IL-6) are significantly associated with a decreased risk of late-onset Alzheimer’s disease. J Neuroinflammation 2012; 9(1): 21–9

    Article  PubMed  CAS  Google Scholar 

  6. Cotman CW, Anderson AJ. A potential role for apoptosis in neurodegeneration and Alzheimer’s disease. Mol Neurobiol 1995; 10: 19–45

    Article  PubMed  CAS  Google Scholar 

  7. Holmes C, Cunningham C, Zotova E, et al. Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology 2011; 77(3): 212–8

    Article  PubMed  CAS  Google Scholar 

  8. Ziabreva I, Perry E, Perry R, et al. Altered neurogenesis in Alzheimer’s disease. J Psychosom Res 2006; 61(3): 311–6

    Article  PubMed  Google Scholar 

  9. Korecka JA, Verhaagen J, Hol EM. Cell-replacement and gene-therapy strategies for Parkinson’s and Alzheimer’s disease. Regen Med 2007; 2(4): 425–46

    Article  PubMed  CAS  Google Scholar 

  10. McClean P, Parthsarathy V, Faivre E, et al. The diabetes drug Liraglutide prevents degenerative processes in a mouse model of Alzheimer’s disease. J Neurosci 2011; 31: 6587–94

    Article  PubMed  CAS  Google Scholar 

  11. Moroo I, Yamada T, Makino H, et al. Loss of insulin receptor immunoreactivity from the substantia nigra pars compacta neurons in Parkinson’s disease. Acta Neuropathol (Berl) 1994; 87(4): 343–8

    Article  CAS  Google Scholar 

  12. Aviles-Olmos I, Limousin P, Lees A, et al. Parkinson’s disease, insulin resistance and novel agents of neuroprotection. Brain. Epub 2012 Feb 17

  13. Strachan MW. Insulin and cognitive function in humans: experimental data and therapeutic considerations. Biochem Soc Trans 2005; 33(Pt 5): 1037–40

    PubMed  CAS  Google Scholar 

  14. Haan MN. Therapy insight: type 2 diabetes mellitus and the risk of late-onset Alzheimer’s disease. Nat Clin Pract Neurol 2006; 2(3): 159–66

    Article  PubMed  CAS  Google Scholar 

  15. Luchsinger JA, Tang MX, Shea S, et al. Hyperinsulinemia and risk of Alzheimer disease. Neurology 2004; 63(7): 1187–92

    Article  PubMed  Google Scholar 

  16. Ristow M. Neurodegenerative disorders associated with diabetes mellitus. J Mol Med 2004; 82(8): 510–29

    Article  PubMed  Google Scholar 

  17. Biessels GJ, De Leeuw FE, Lindeboom J, et al. Increased cortical atrophy in patients with Alzheimer’s disease and type 2 diabetes mellitus. J Neurol Neurosurg Psychiatry 2006; 77(3): 304–7

    Article  PubMed  CAS  Google Scholar 

  18. Janson J, Laedtke T, Parisi J, et al. Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 2004; 53: 474–81

    Article  PubMed  CAS  Google Scholar 

  19. Carro E, Torres-Aleman I. Insulin-like growth factor I and Alzheimer’s disease: therapeutic prospects? Expert Rev Neurother 2004; 4(1): 79–86

    Article  PubMed  CAS  Google Scholar 

  20. Hoyer S. Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J Pharmacol 2004; 490(1–3): 115–25

    Article  PubMed  CAS  Google Scholar 

  21. Steen E, Terry BM, Rivera E, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease: is this type 3 diabetes? J Alzheimers Dis 2005; 7(1): 63–80

    PubMed  CAS  Google Scholar 

  22. Lester-Coll N, Rivera EJ, Soscia SJ, et al. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer’s disease. J Alzheimers Dis 2006; 9(1): 13–33

    PubMed  CAS  Google Scholar 

  23. Talbot K, Wang HY, Kazi H, et al. Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest 2012; 122(4): 1316–38

    Article  PubMed  CAS  Google Scholar 

  24. Moloney AM, Griffin RJ, Timmons S, et al. Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer’s disease indicate possible resistance to IGF-1 and insulin signalling. Neurobiol Aging 2010; 31(2): 224–43

    Article  PubMed  CAS  Google Scholar 

  25. Klein W, Barlow A, Chrimy B, et al., editors. “ADDLS”-soluble Ab oligomers that cause biphasic loss of hippocampal neuron function and survival. Society for Neuroscience 27th Annual Meeting; 1997 Oct 25–29; New Orleans (LA)

    Google Scholar 

  26. De Felice FG, Vieira MN, Bomfim TR, et al. Protection of synapses against Alzheimer’s-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A 2009; 106(6): 1971–6

    Article  PubMed  Google Scholar 

  27. Morris JK, Zhang H, Gupte AA, et al. Measures of striatal insulin resistance in a 6-hydroxydopamine model of Parkinson’s disease. Brain Res 2008; 1240: 185–95

    Article  PubMed  CAS  Google Scholar 

  28. Morris JK, Bomhoff GL, Gorres BK, et al. Insulin resistance impairs nigrostriatal dopamine function. Exp Neurol 2011; 231(1): 171–80

    Article  PubMed  CAS  Google Scholar 

  29. Benomar Y, Naour N, Aubourg A, et al. Insulin and leptin induce Glut4 plasma membrane translocation and glucose uptake in a human neuronal cell line by a phosphatidylinositol 3-kinase-dependent mechanism. Endocrinology 2006; 147(5): 2550–6

    Article  PubMed  CAS  Google Scholar 

  30. Grillo CA, Piroli GG, Hendry RM, et al. Insulin-stimulated translocation of GLUT4 to the plasma membrane in rat hippocampus is PI3-kinase dependent. Brain Res 2009; 1296: 35–45

    Article  PubMed  CAS  Google Scholar 

  31. Hoyer S. Models of Alzheimer’s disease: cellular and molecular aspects. J Neural Transm 1997; 49(11): 11–21

    CAS  Google Scholar 

  32. Biessels GJ, Bravenboer B, Gispen WH. Glucose, insulin and the brain: modulation of cognition and synaptic plasticity in health and disease: a preface. Eur J Pharmacol 2004; 490(1–3): 1–4

    Article  PubMed  CAS  Google Scholar 

  33. Zhao AZ, Shinohara MM, Huang D, et al. Leptin induces insulin-like signaling that antagonizes cAMP elevation by glucagon in hepatocytes. J Biol Chem 2000; 275(15): 11348–54

    Article  PubMed  CAS  Google Scholar 

  34. de la Monte SM, Wands JR. Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer’s disease. J Alzheimers Dis 2006; 9(2): 167–81

    PubMed  Google Scholar 

  35. Hölscher C. Synaptic plasticity and learning and memory: LTP and beyond. J Neurosci Res 1999; 58: 62–75

    Article  PubMed  Google Scholar 

  36. Stockhorst U, de Fries D, Steingrueber HJ, et al. Insulin and the CNS: effects on food intake, memory, and endocrine parameters and the role of intranasal insulin administration in humans. Physiol Behav 2004; 83(1): 47–54

    PubMed  CAS  Google Scholar 

  37. Holscher C. Development of beta-amyloid-induced neurodegeneration in Alzheimer’s disease and novel neuroprotective strategies. Rev Neurosci 2005; 16(3): 181–212

    PubMed  CAS  Google Scholar 

  38. Li L, Hölscher C. Common pathological processes in Alzheimer disease and type 2 diabetes: a review. Brain Res Rev 2007; 56: 384–402

    Article  PubMed  CAS  Google Scholar 

  39. van Dam P, Aleman A. Insulin-like growth factor-I, cognition and brain aging. Eur J Pharmacol 2004; 490(1–3): 87–95

    PubMed  Google Scholar 

  40. Carro E, Torres AI. The role of insulin and insulin-like growth factor I in the molecular and cellular mechanisms underlying the pathology of Alzheimer’s disease. Eur J Pharmacol 2004; 490(1–3): 127–33

    Article  PubMed  CAS  Google Scholar 

  41. Watson GS, Craft S. Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer’s disease. Eur J Pharmacol 2004; 490(1–3): 97–113

    Article  PubMed  CAS  Google Scholar 

  42. Zhao WQ, Chen H, Quon MJ, et al. Insulin and the insulin receptor in experimental models of learning and memory. Eur J Pharmacol 2004; 490(1–3): 71–81

    Article  PubMed  CAS  Google Scholar 

  43. Reger MA, Watson GS, Green PS, et al. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-beta in memory-impaired older adults. J Alzheimers Dis 2008; 13(3): 323–31

    PubMed  CAS  Google Scholar 

  44. Okereke OI, Selkoe DJ, Pollak MN, et al. A profile of impaired insulin degradation in relation to late-life cognitive decline: a preliminary investigation. Int J Geriatr Psychiatry 2008; 24: 177–82

    Article  Google Scholar 

  45. Reger MA, Watson GS, Green PS, et al. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 2008; 70(6): 440–8

    Article  PubMed  CAS  Google Scholar 

  46. Craft S. Insulin resistance and Alzheimer’s disease pathogenesis: potential mechanisms and implications for treatment. Curr Alzheimer Res 2007; 4(2): 147–52

    Article  PubMed  CAS  Google Scholar 

  47. Craft S. A randomized, placebo-controlled trial of intranasal insulin in amnestic MCI and early Alzheimer’s [abstract no. P3-455]. ICAD Conference; 2010 Jul 10-15; Honolulu (HI)

    Google Scholar 

  48. Holscher C. Incretin analogues that have been developed to treat type 2 diabetes hold promise as a novel treatment strategy for Alzheimer’s disease. Recent Pat CNS Drug Discov 2010; 5: 109–17

    Article  PubMed  CAS  Google Scholar 

  49. Holscher C, Li L. New roles for insulin-like hormones in neuronal signalling and protection: new hopes for novel treatments of Alzheimer’s disease? Neurobiol Aging 2010; 31: 1495–502

    Article  PubMed  Google Scholar 

  50. Holscher C. Diabetes as a risk factor for Alzheimer’s disease: insulin signalling impairment in the brain as an alternative model of Alzheimer’s disease. Biochem Soc Trans 2011; 39(4): 891–7

    Article  PubMed  Google Scholar 

  51. Drucker DJ, Nauck MA. The incretin system: glucagonlike peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006; 368(9548): 1696–705

    Article  PubMed  CAS  Google Scholar 

  52. Holst JJ. Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors. Expert Opin Emerg Drugs 2004; 9(1): 155–66

    Article  PubMed  CAS  Google Scholar 

  53. Green BD, Gault VA, Flatt PR, et al. Comparative effects of GLP-1 and GIP on cAMP production, insulin secretion, and in vivo antidiabetic actions following substitution of Ala8/Ala2 with 2-aminobutyric acid. Arch Biochem Biophys 2004; 428(2): 136–43

    Article  PubMed  CAS  Google Scholar 

  54. Green BD, Flatt PR. Incretin hormone mimetics and analogues in diabetes therapeutics. Best Pract Res Clin Endocrinol Metab 2007; 21(4): 497–516

    Article  PubMed  CAS  Google Scholar 

  55. During MJ, Cao L, Zuzga DS, et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med 2003; 9(9): 1173–9

    Article  PubMed  CAS  Google Scholar 

  56. Perry T, Holloway HW, Weerasuriya A, et al. Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp Neurol 2007; 203(2): 293–301

    Article  PubMed  CAS  Google Scholar 

  57. Hamilton A, Holscher C. Receptors for the insulin-like peptide GLP-1 are expressed on neurons in the CNS. Neuroreport 2009; 20: 1161–6

    Article  PubMed  CAS  Google Scholar 

  58. Iwai T, Ito S, Tanimitsu K, et al. Glucagon-like peptide-1 inhibits LPS-induced IL-1beta production in cultured rat astrocytes. Neurosci Res 2006; 55(4): 352–60

    Article  PubMed  CAS  Google Scholar 

  59. Gault V, Holscher C. GLP-1 agonists facilitate hippocampal LTP and reverse the impairment of LTP induced by betaamyloid. Eur J Pharmacol 2008; 587: 112–7

    Article  PubMed  CAS  Google Scholar 

  60. Kastin AJ, Akerstrom V. Entry of exendin-4 into brain is rapid but may be limited at high doses. Int J Obes Relat Metab Disord 2003; 27(3): 313–8

    Article  PubMed  CAS  Google Scholar 

  61. Kastin AJ, Akerstrom V, Pan W. Interactions of glucagonlike peptide-1 (GLP-1) with the blood-brain barrier. J Mol Neurosci 2002; 18(1–2): 7–14

    Article  PubMed  CAS  Google Scholar 

  62. Hunter K, Holscher C. Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis. BMC Neurosci 2012; 13(1): 33–8

    Article  PubMed  CAS  Google Scholar 

  63. McGovern S, Kerry H, Holscher C. Effects of the glucagonlike polypeptide-1 analogue (Val 8)GLP-1 on learning, progenitor cell proliferation and neurogenesis in the C57B/16 mouse brain. Brain Res. In press

  64. Gengler S, McClean P, McCurtin R, et al. Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice. Neurobiol Aging 2012; 33: 265–76

    Article  PubMed  CAS  Google Scholar 

  65. Wang XH, Li L, Holscher C, et al. Val 8-glucagon-like peptide-1 protects against Abeta1-40-induced impairment of hippocampal late-phase long-term potentiation and spatial learning in rats. Neuroscience 2010; 170(4): 1239–48

    Article  PubMed  CAS  Google Scholar 

  66. Han W-N, Holscher C, Yuan L, et al. Liraglutide protects against amyloid-X protein-induced impairment of spatial learning and memory in rats. Neurobiol Aging. Epub 2012 May 14

  67. Courreges JP, Vilsboll T, Zdravkovic M, et al. Beneficial effects of once-daily liraglutide, a human glucagon-like peptide-1 analogue, on cardiovascular risk biomarkers in patients with type 2 diabetes. Diabet Med 2008; 25(9): 1129–31

    Article  PubMed  Google Scholar 

  68. McClean PL, Gault VA, Harriott P, et al. Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: a link between diabetes and Alzheimer’s disease. Eur J Pharmacol 2010; 630: 158–62

    Article  PubMed  CAS  Google Scholar 

  69. Perry T, Haughey NJ, Mattson MP, et al. Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. J Pharmacol Exp Ther 2002; 302(3): 881–8

    Article  PubMed  CAS  Google Scholar 

  70. Perry T, Lahiri DK, Sambamurti K, et al. Glucagon-like peptide-1 decreases endogenous amyloid-beta peptide (Abeta) levels and protects hippocampal neurons from death induced by Abeta and iron. J Neurosci Res 2003; 72(5): 603–12

    Article  PubMed  CAS  Google Scholar 

  71. Li Y, Duffy K, Ottinger M, et al. GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer’s disease. J Alzheimers Dis 2010; 19: 1205–19

    PubMed  Google Scholar 

  72. Porter DW, Irwin N, Flatt PR, et al. Prolonged GIP receptor activation improves cognitive function, hippocampal synaptic plasticity and glucose homeostasis in high-fat fed mice. Eur J Pharmacol 2010; 650(2–3): 688–93

    PubMed  Google Scholar 

  73. Porter DW, Kerr BD, Flatt PR, et al. Four weeks administration of liraglutide improves memory and learning as well as glycaemic control in mice with high fat dietary-induced obesity and insulin resistance. Diabetes Obes Metab 2010; 12(10): 891–9

    Article  PubMed  CAS  Google Scholar 

  74. Hamilton A, Patterson S, Porter D, et al. Novel GLP-1 mimetics developed to treat type 2 diabetes promote progenitor cell proliferation in the brain. J Neurosci Res 2011; 89(4): 481–9

    Article  PubMed  CAS  Google Scholar 

  75. Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci 2007; 30(9): 464–72

    Article  PubMed  CAS  Google Scholar 

  76. Bradbury J. Hope for AD with NGF gene-therapy trial. Lancet Neurol 2005; 4(6): 335–42

    Article  PubMed  Google Scholar 

  77. Azzouz M, Ralph GS, Storkebaum E, et al. VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model. Nature 2004; 429(6990): 413–7

    Article  PubMed  CAS  Google Scholar 

  78. Gregory-Evans K, Chang F, Hodges MD, et al. Ex vivo gene therapy using intravitreal injection of GDNF-secreting mouse embryonic stem cells in a rat model of retinal degeneration. Mol Vis 2009; 15: 962–73

    PubMed  CAS  Google Scholar 

  79. Bertilsson G, Patrone C, Zachrisson O, et al. Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson’s disease. J Neurosci Res 2008; 86(2): 326–38

    Article  PubMed  CAS  Google Scholar 

  80. Harkavyi A, Abuirmeileh A, Lever R, et al. Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson’s disease. J Neuroinflammation 2008; 5: 19–31

    Article  PubMed  Google Scholar 

  81. Li Y, Perry T, Kindy MS, et al. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc Natl Acad Sci U S A 2009; 106(4): 1285–90

    Article  PubMed  CAS  Google Scholar 

  82. Pressley JC, Louis ED, Tang MX, et al. The impact of comorbid disease and injuries on resource use and expenditures in parkinsonism. Neurology 2003; 60(1): 87–93

    Article  PubMed  CAS  Google Scholar 

  83. Kunst C. Complex genetics of amyotrophic lateral sclerosis. Am J Hum Genet 2004; 75: 933–47

    Article  PubMed  CAS  Google Scholar 

  84. Li Y, Chigurupati S, Holloway HW, et al. Exendin-4 ameliorates motor neuron degeneration in cellular and animal models of amyotrophic lateral sclerosis. PLoS One 2012; 7(2): e32008

    Article  PubMed  CAS  Google Scholar 

  85. Knippenberg S, Thau N, Dengler R, et al. Intracerebroventricular injection of encapsulated human mesenchymal cells producing glucagon-like peptide-1 prolongs survival in a mouse model of ALS. PLoS ONE 2012; 7(6): e36857

    Article  PubMed  CAS  Google Scholar 

  86. Himeno T, Kamiya H, Naruse K, et al. Beneficial effects of exendin-4 on experimental polyneuropathy in diabetic mice. Diabetes 2011; 60(9): 2397–406

    Article  PubMed  CAS  Google Scholar 

  87. Ayasolla K, Khan M, Singh AK, et al. Inflammatory mediator and beta-amyloid (25–35)-induced ceramide generation and iNOS expression are inhibited by vitamin E. Free Radic Biol Med 2004; 37(3): 325–38

    Article  PubMed  CAS  Google Scholar 

  88. Arakawa M, Mita T, Azuma K, et al. Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4. Diabetes 2010; 59(4): 1030–7

    Article  PubMed  CAS  Google Scholar 

  89. Dozier KC, Cureton EL, Kwan RO, et al. Glucagon-like peptide-1 protects mesenteric endothelium from injury during inflammation. Peptides 2009; 30(9): 1735–41

    Article  PubMed  CAS  Google Scholar 

  90. Parsarathy V, Holscher C, editors. The novel GLP1 analogue, liraglutide, reduces inflammation in a mouse model of brain tissue injury. Washington, DC: Society for Neuroscience Annual Meeting, 2011

    Google Scholar 

  91. Lee CH, Yan B, Yoo KY, et al. Ischemia-induced changes in glucagon-like peptide-1 receptor and neuroprotective effect of its agonist, exendin-4, in experimental transient cerebral ischemia. J Neurosci Res 2011; 89(7): 1103–13

    Article  PubMed  CAS  Google Scholar 

  92. Teramoto S, Miyamoto N, Yatomi K, et al. Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia. J Cereb Blood Flow Metab 2011; 31(8): 1696–705

    Article  PubMed  CAS  Google Scholar 

  93. Rossi S, Furlan R, De Chiara V, et al. Interleukin-1beta causes synaptic hyperexcitability in multiple sclerosis. Ann Neurol 2012; 71(1): 76–83

    Article  PubMed  CAS  Google Scholar 

  94. Arnon R, Aharoni R. Neuroprotection and neurogeneration in MS and its animal model EAE effected by glatiramer acetate. J Neural Transm 2009; 116(11): 1443–9

    Article  PubMed  CAS  Google Scholar 

  95. Aharoni R, Vainshtein A, Stock A, et al. Distinct pathological patterns in relapsing-remitting and chronic models of experimental autoimmune enchephalomyelitis and the neuroprotective effect of glatiramer acetate. J Autoimmun 2011; 37(3): 228–41

    Article  PubMed  CAS  Google Scholar 

  96. Nauck MA. Incretin-based therapies for type 2 diabetes mellitus: properties, functions, and clinical implications. Am J Med 2011; 124(1 Suppl.): S3–18

    Article  PubMed  CAS  Google Scholar 

  97. Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev 2012; 33(2): 187–215

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Part of the work described here was funded by the Alzheimer Research UK and the Alzheimer Society UK charities. Prof. Holscher has been a consultant and invited speaker for the following drug companies: NovoNordisk, Novartis, Sanofi, Eli Lilly and Merck. He is a named inventor on two patent applications for the use of GLP-1 analogues in neurodegenerative diseases.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christian Hölscher PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hölscher, C. Potential Role of Glucagon-Like Peptide-1 (GLP-1) in Neuroprotection. CNS Drugs 26, 871–882 (2012). https://doi.org/10.2165/11635890-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11635890-000000000-00000

Keywords

Navigation