Glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide analogues as novel treatments for Alzheimer's and Parkinson's disease

Cardiovascular Endocrinology

Volumn 5, Issue 3, 2016, Pages 93-98

  Hölscher, Christian ^a  

^a LANCASTER UNIVERSITY   (United Kingdom)

Author keywords

growth factors; incretins; insulin; neurodegeneration

Indexed keywords

EXENDIN 4; FLUORODEOXYGLUCOSE F 18; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON LIKE PEPTIDE 1; INSULIN; LIRAGLUTIDE;

ALZHEIMER DISEASE; COGNITIVE DEFECT; HUMAN; MOTOR DYSFUNCTION; NEUROPROTECTION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PARKINSON DISEASE; PILOT STUDY; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SIGNAL TRANSDUCTION;

EID: 85000702111     PISSN: None     EISSN: 2162688X     Source Type: Journal    
DOI: 10.1097/XCE.0000000000000087     Document Type: Review

References (93)

1. Moroo I, Yamada T, Makino H, Tooyama I, McGeer PL, McGeer EG, Hirayama K. Loss of insulin receptor immunoreactivity from the substantia nigra pars compacta neurons in Parkinsons disease. Acta Neuropathol 1994; 87:343-348.
2. Aviles-Olmos I, Limousin P, Lees A, Foltynie T. Parkinsons disease, insulin resistance and novel agents of neuroprotection. Brain 2013; 136 (Pt 2): 374-384.
3. Strachan MW. Insulin and cognitive function in humans: experimental data and therapeutic considerations. Biochem Soc Trans 2005; 33 (Pt 5): 1037-1040.
4. Haan MN. Therapy insight: type 2 diabetes mellitus and the risk of late-onset Alzheimers disease. Nat Clin Pract Neurol 2006; 2:159-166.
5. Luchsinger JA, Tang MX, Shea S, Mayeux R. Hyperinsulinemia and risk of Alzheimer disease. Neurology 2004; 63:1187-1192.
6. Ristow M. Neurodegenerative disorders associated with diabetes mellitus. J Mol Med (Berl) 2004; 82:510-529.
7. Biessels GJ, De Leeuw FE, Lindeboom J, Barkhof F, Scheltens P. Increased cortical atrophy in patients with Alzheimers disease and type 2 diabetes mellitus. J Neurol Neurosurg Psychiatry 2006; 77:304-307.
8. Leibson CL, Rocca WA, Hanson VA, Cha R, Kokmen E, OBrien PC, Palumbo PJ. Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol 1997; 145:301-308.
9. Janson J, Laedtke T, Parisi JE, OBrien P, Petersen RC, Butler PC. Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 2004; 53:474-481.
10. Ohara T, Doi Y, Ninomiya T, Hirakawa Y, Hata J, Iwaki T, et al. Glucose tolerance status and risk of dementia in the community: the Hisayama study. Neurology 2011; 77:1126-1134.
11. Schrijvers EM, Witteman JC, Sijbrands EJ, Hofman A, Koudstaal PJ, Breteler MM. Insulin metabolism and the risk of Alzheimer disease: the Rotterdam study. Neurology 2010; 75:1982-1987.
12. Hu G, Jousilahti P, Bidel S, Antikainen R, Tuomilehto J. Type 2 diabetes and the risk of Parkinsons disease. Diabetes Care 2007; 30:842-847.
13. Cereda E, Barichella M, Cassani E, Caccialanza R, Pezzoli G. Clinical features of Parkinson disease when onset of diabetes came first: a case-control study. Neurology 2012; 78:1507-1511.
14. Cereda E, Barichella M, Pedrolli C, Klersy C, Cassani E, Caccialanza R, Pezzoli G. Diabetes and risk of Parkinsons disease: a systematic review and meta-analysis. Diabetes Care 2011; 34:2614-2623.
15. Lu L, Fu DL, Li HQ, Liu AJ, Li JH, Zheng GQ. Diabetes and risk of Parkinsons disease: an updated meta-analysis of case-control studies. PLoS One 2014; 9:e85781.
16. Lima MM, Targa AD, Noseda AC, Rodrigues LS, Delattre AM, dos Santos FV, et al. Does Parkinsons disease and type-2 diabetes mellitus present common pathophysiological mechanisms and treatments? CNS Neurol Disord Drug Targets 2014; 13:418-428.
17. Steen E, Terry BM, Rivera EJ, Cannon JL, Neely TR, Tavares R, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimers disease -is this type 3 diabetes? J Alzheimers Dis 2005; 7:63-80.
18. Lester-Coll N, Rivera EJ, Soscia SJ, Doiron K, Wands JR, de la Monte SM. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimers disease. J Alzheimers Dis 2006; 9:13-33.
19. Talbot K, Wang HY, Kazi H, Han LY, Bakshi KP, Stucky A, et al. Demonstrated brain insulin resistance in Alzheimers disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest 2012; 122:1316-1338.
20. Moloney AM, Griffin RJ, Timmons S, OConnor R, Ravid R, ONeill C. Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimers disease indicate possible resistance to IGF-1 and insulin signalling. Neurobiol Aging 2010; 31:224-243.
21. Morris JK, Zhang H, Gupte AA, Bomhoff GL, Stanford JA, Geiger PC. Measures of striatal insulin resistance in a 6-hydroxydopamine model of Parkinsons disease. Brain Res 2008; 1240:185-195.
22. Pellecchia MT, Santangelo G, Picillo M, Pivonello R, Longo K, Pivonello C, et al. Insulin-like growth factor-1 predicts cognitive functions at 2-year followup in early, drug-nave Parkinsons disease. Eur J Neurol 2014; 21:802-807.
23. Morris JK, Bomhoff GL, Gorres BK, Davis VA, Kim J, Lee PP, et al. Insulin resistance impairs nigrostriatal dopamine function. Exp Neurol 2011; 231:171-180.
24. Numao A, Suzuki K, Miyamoto M, Miyamoto T, Hirata K. Clinical correlates of serum insulin-like growth factor-1 in patients with Parkinsons disease, multiple system atrophy and progressive supranuclear palsy. Parkinsonism Relat Disord 2014; 20:212-216.
25. Banks WA. The source of cerebral insulin. Eur J Pharmacol 2004; 490:5-12.
26. Fernando RN, Albiston AL, Chai SY. The insulin-regulated aminopeptidase IRAP is colocalised with GLUT4 in the mouse hippocampus -potential role in modulation of glucose uptake in neurones? Eur J Neurosci 2008; 28:588-598.
27. Ghasemi R, Haeri A, Dargahi L, Mohamed Z, Ahmadiani A. Insulin in the brain: sources, localization and functions. Mol Neurobiol 2013; 47:145-1171.
28. Carro E, Torres-Aleman I. The role of insulin and insulin-like growth factor I in the molecular and cellular mechanisms underlying the pathology of Alzheimers disease. Eur J Pharmacol 2004; 490:127-133.
29. Craft S, Cholerton B, Baker LD. Insulin and Alzheimers disease: untangling the web. J Alzheimers Dis 2013; 33 (Suppl 1):S263-S275.
30. Hoyer S. Glucose metabolism and insulin receptor signal transduction in Alzheimer disease. Eur J Pharmacol 2004; 490:115-125.
31. Holscher C. Insulin, incretins and other growth factors as potential novel treatments for Alzheimers and Parkinsons diseases. Biochem Soc Trans 2014; 42:593-599.
32. Watson GS, Craft S. Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimers disease. Eur J Pharmacol 2004; 490:97-113.
33. Zhao WQ, Chen H, Quon MJ, Alkon DL. Insulin and the insulin receptor in experimental models of learning and memory. Eur J Pharmacol 2004; 490:71-81.
34. Reger MA, Watson GS, Green PS, Baker LD, Cholerton B, Fishel MA, et al. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-beta in memory-impaired older adults. J Alzheimers Dis 2008; 13:323-331.
35. Okereke OI, Selkoe DJ, Pollak MN, Stampfer MJ, Hu FB, Hankinson SE, Grodstein F. A profile of impaired insulin degradation in relation to late-life cognitive decline: a preliminary investigation. Int J Geriatr Psychiatry 2009; 24:177-1182.
36. Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, et al. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 2008; 70:440-448.
37. Craft S. Insulin resistance and Alzheimers disease pathogenesis: potential mechanisms and implications for treatment. Curr Alzheimer Res 2007; 4:147-152.
38. Craft S. A randomized, placebo-controlled trial of intranasal insulin in amnestic MCI and early Alzheimers. Hawaii, USA: ICAD conference; 10-15 July 2010. Abstract P3-P455.
39. Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol 2012; 69:29-38.
40. Claxton A, Baker LD, Hanson A, Trittschuh EH, Cholerton B, Morgan A, et al. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimers disease dementia. J Alzheimers Dis 2015; 44:897-906.
41. Freiherr J, Hallschmid M, Frey WH II, Brunner YF, Chapman CD, Holscher C, et al. Intranasal insulin as a treatment for Alzheimers disease: a review of basic research and clinical evidence. CNS Drugs 2013; 27:505-514.
42. Holscher C. First clinical data of the neuroprotective effects of nasal insulin application in patients with Alzheimers disease. Alzheimers Dement 2014 (Suppl) S33-S37.
43. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007; 132:2131-2157.
44. Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab 2013; 17:819-837.
45. Lean ME, Carraro R, Finer N, Hartvig H, Lindegaard ML, Rossner S, et al. NN8022-1807 Investigators. Tolerability of nausea and vomiting and associations with weight loss in a randomized trial of liraglutide in obese, non-diabetic adults. Int J Obes (Lond) 2014; 38:689-697.
46. Baggio LL, Kim JG, Drucker DJ. Chronic exposure to GLP-1R agonists promotes homologous GLP-1 receptor desensitization in vitro but does not attenuate GLP-1R-dependent glucose homeostasis in vivo. Diabetes 2004 (Suppl 3) S205-S214.
47. Banks WA, Jaspan JB, Kastin AJ. Selective, physiological transport of insulin across the blood-brain barrier: novel demonstration by species-specific radioimmunoassays. Peptides 1997; 18:1257-1262.
48. Kastin AJ, Akerstrom V, Pan W. Interactions of glucagon-like peptide-1 (GLP-1) with the blood-brain barrier. J Mol Neurosci 2002; 18:7-14.
49. 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; 27:313-318.
50. Hunter K, Holscher C. Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis. BMC Neurosci 2012; 13:33.
51. Secher A, Jelsing J, Baquero AF, Hecksher-Sorensen J, Cowley MA, Dalboge LS, et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest 2014; 124:4473-4488.
52. 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; 403:261-280.
53. Teramoto S, Miyamoto N, Yatomi K, Tanaka Y, Oishi H, Arai H, 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; 31:1696-1705.
54. Darsalia V, Ortsater H, Olverling A, Darlof E, Wolbert P, Nystrom T, et al. The DPP-4 inhibitor linagliptin counteracts stroke in the normal and diabetic mouse brain: a comparison with glimepiride. Diabetes 2013; 62:1289-1296.
55. Darsalia V, Mansouri S, Ortsater H, Olverling A, Nozadze N, Kappe C, et al. Glucagon-like peptide-1 receptor activation reduces ischaemic brain damage following stroke in Type 2 diabetic rats. Clin Sci (Lond) 2012; 122:473-483.
56. Lee CH, Yan B, Yoo KY, Choi JH, Kwon SH, Her S, 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; 89:1103-1113.
57. During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med 2003; 9:1173-1171179.
58. Hamilton A, Holscher C. Receptors for the insulin-like peptide GLP-1 are expressed on neurons in the CNS. Neuroreport 2009; 20:1161-1166.
59. Li Y, Perry T, Kindy MS, Harvey BK, Tweedie D, Holloway HW, 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 USA 2009; 106:1285-1290.
60. Drucker DJ. Incretin action in the pancreas: potential promise, possible perils, and pathological pitfalls. Diabetes 2013; 62:3316-3323.
61. Cork SC, Richards JE, Holt MK, Gribble FM, Reimann F, Trapp S. Distribution and characterisation of glucagon-like peptide-1 receptor expressing cells in the mouse brain. Mol Metab 2015; 4:718-731.
62. Courreges JP, Vilsboll T, Zdravkovic M, Le-Thi T, Krarup T, Schmitz O, 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; 25:1129-1131.
63. McClean PL, Parthsarathy V, Faivre E, Holscher C. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimers disease. J Neurosci 2011; 31:6587-6594.
64. McClean PL, Holscher C. Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimers disease. Neuropharmacology 2014; 76 (Pt A):57-67.
65. McClean PL, Jalewa J, Holscher C. Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice. Behav Brain Res 2015; 293:96-106.
66. McClean PL, Holscher C. Lixisenatide, a drug developed to treat type 2 diabetes, shows neuroprotective effects in a mouse model of Alzheimers disease. Neuropharmacology 2014; 86:241-258.
67. Hansen HH, Barkholt P, Fabricius K, Jelsing J, Terwel D, Pyke C, et al. The GLP-1 receptor agonist liraglutide reduces pathology-specific tau phosphorylation and improves motor function in a transgenic hTauP301L mouse model of tauopathy. Brain Res 2016; 1634:158-170.
68. Hansen HH, Fabricius K, Barkholt P, Niehoff ML, Morley JE, Jelsing J, et al. The GLP-1 receptor agonist liraglutide improves memory function and increases hippocampal CA1 neuronal numbers in a senescence-accelerated mouse model of alzheimers disease. J Alzheimers Dis 2015; 46:877-888.
69. Li Y, Duffy KB, Ottinger MA, Ray B, Bailey JA, Holloway HW, et al. GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimers disease. J Alzheimers Dis 2010; 19:1205-1219.
70. Perry T, Greig NH. Enhancing central nervous system endogenous GLP-1 receptor pathways for intervention in Alzheimers disease. Curr Alzheimer Res 2005; 2:377-385.
71. Rachmany L, Tweedie D, Li Y, Rubovitch V, Holloway HW, Miller J, et al. Exendin-4 induced glucagon-like peptide-1 receptor activation reverses behavioral impairments of mild traumatic brain injury in mice. Age (Dordr) 2013; 35:1621-1636.
72. Eakin K, Li Y, Chiang YH, Hoffer BJ, Rosenheim H, Greig NH, Miller JP. Exendin-4 ameliorates traumatic brain injury-induced cognitive impairment in rats. PLoS One 2013; 8:e82016.
73. Perry T, Holloway HW, Weerasuriya A, Mouton PR, Duffy K, Mattison JA, Greig NH. Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp Neurol 2007; 203:293-301.
74. Porter DW, Irwin N, Flatt PR, Holscher C, Gault VA. Prolonged GIP receptor activation improves cognitive function, hippocampal synaptic plasticity and glucose homeostasis in high-fat fed mice. Eur J Pharmacol 2011; 650:688-693.
75. Porter DW, Kerr BD, Flatt PR, Holscher C, Gault VA. 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; 12:891-899.
76. Hamilton A, Patterson S, Porter D, Gault VA, Holscher C. Novel GLP-1 mimetics developed to treat type 2 diabetes promote progenitor cell proliferation in the brain. J Neurosci Res 2011; 89:481-489.
77. Faivre E, Holscher C. D-Ala2GIP facilitated synaptic plasticity and reduces plaque load in aged wild type mice and in an Alzheimers disease mouse model. J Alzheimers Dis 2013; 35:267-283.
78. Faivre E, Holscher C. Neuroprotective effects of D-Ala(2)GIP on Alzheimers disease biomarkers in an APP/PS1 mouse model. Alzheimers Res Ther 2013; 5:20.
79. Duffy AM, Holscher C. The incretin analogue D-Ala2GIP reduces plaque load, astrogliosis and oxidative stress in an APP/PS1 mouse model of Alzheimers disease. Neuroscience 2013; 228:294-300.
80. Bertilsson G, Patrone C, Zachrisson O, Andersson A, Dannaeus K, Heidrich J, et al. Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinsons disease. J Neurosci Res 2008; 86:326-338.
81. Harkavyi A, Abuirmeileh A, Lever R, Kingsbury AE, Biggs CS, Whitton PS. Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinsons disease. J Neuroinflammation 2008; 5:19.
82. Liu W, Jalewa J, Sharma M, Li G, Li L, Holscher C. Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinsons disease. Neuroscience 2015; 303:42-50.
83. Li Y, Liu W, Li L, Holscher C. Neuroprotective effects of a GIP analogue in the MPTP Parkinsons disease mouse model. Neuropharmacology 2016; 101:255-263.
84. Finan B, Ma T, Ottaway N, et al. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci Transl Med 2013; 5:209ra151.
85. Cao L, Li D, Feng P, Li L, Xue GF, Li G, Holscher C. A novel dual GLP-1 and GIP incretin receptor agonist is neuroprotective in a mouse model of Parkinsons disease by reducing chronic inflammation in the brain. Neuroreport 2016; 27:384-391.
86. Ji C, Xue GF, Lijun C, Feng P, Li D, Li L, et al. A novel dual GLP-1 and GIP receptor agonist is neuroprotective in the MPTP mouse model of Parkinsons disease by increasing expression of BDNF. Brain Res 2016; 1634:1-11.
87. Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Muller FJ, Loring JF, et al. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci USA 2009; 106:13594-13599.
88. Allen SJ, Watson JJ, Shoemark DK, Barua NU, Patel NK. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther 2013; 138:155-175.
89. Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Ell P, Soderlund T, et al. Exenatide and the treatment of patients with Parkinsons disease. J Clin Invest 2013; 123:2730-2736.
90. Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Kahan J, Ell P, et al. Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinsons disease. J Parkinsons Dis 2014; 4:337-344.
91. Egefjord L, Gejl M, Moller A, Brndgaard H, Gottrup H, Antropova O, et al. Effects of liraglutide on neurodegeneration, blood flow and cognition in Alzheimers disease -protocol for a controlled, randomized doubleblinded trial. Dan Med J 2012; 59:A4519.
92. Femminella GD, Edison P. Evaluation of neuroprotective effect of glucagonlike peptide 1 analogs using neuroimaging. Alzheimers Dement 2014; 10 (Suppl):S55-S61.
93. Gejl M, Gjedde A, Egefjord L, Moller A, Hansen SB, Vang K, et al. In Alzheimers disease, six-month treatment with GLP-1 analogue prevents decline of brain glucose metabolism: randomized, placebo-controlled, double-blind clinical trial. Front Aging Neurosci 2016; 8:108.