Drogi użytkowniku, aplikacja do prawidłowego działania wymaga obsługi JavaScript. Proszę włącz obsługę JavaScript w Twojej przeglądarce.

Przeglądasz jako GOŚĆ
Tytuł pozycji:

Brain insulin, insulin-like growth factor 1 and glucagon-like peptide 1 signalling in Alzheimer's disease.

Tytuł :
Brain insulin, insulin-like growth factor 1 and glucagon-like peptide 1 signalling in Alzheimer's disease.
Autorzy :
Ferreira ST; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Pokaż więcej
Źródło :
Journal of neuroendocrinology [J Neuroendocrinol] 2021 Apr; Vol. 33 (4), pp. e12959. Date of Electronic Publication: 2021 Mar 19.
Typ publikacji :
Journal Article; Review
Język :
Imprint Name(s) :
Publication: <2010->: Malden, MA : Wiley & Sons
Original Publication: Eynsham, Oxon, UK : Oxford University Press, c1989-
References :
Cunnane SC, Trushina E, Morland C, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020;19:609-633.
Holman GD. Structure, function and regulation of mammalian glucose transporters of the SLC2 family. Pflugers Arch. 2020;472:1155-1175.
Koepsell H. Glucose transporters in brain in health and disease. Pflugers Arch. 2020;472:1299-1343.
Banks WA. The source of cerebral insulin. Eur J Pharmacol. 2004;490:5-12.
Laron Z. Insulin and the brain. Arch Physiol Biochem. 2009;115:112-116.
Blázquez E, Velázquez E, Hurtado-Carneiro V, Ruiz-Albusac JM. Insulin in the brain: its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer's disease. Front Endocrinol. 2014;5:161.
Woods SC, Seeley RJ, Baskin DG, Schwartz MW. Insulin and the blood-brain barrier. Curr Pharm Des. 2003;9:795-800.
Duarte AI, Moreira PI, Oliveira CR. Insulin in central nervous system: more than just a peripheral hormone. J Aging Res. 2012;2012:384017.
Heni M, Kullmann S, Preissl H, Fritsche A, Häring HU. Impaired insulin action in the human brain: causes and metabolic consequences. Nat Rev Endocrinol. 2015;11:701-711.
Kleinridders A, Ferris HA, Cai W, Kahn CR. Insulin action in brain regulates systemic metabolism and brain function. Diabetes. 2014;63:2232-2243.
Kullmann S, Kleinridders A, Small DM, et al. Central nervous pathways of insulin action in the control of metabolism and food intake. Lancet Diabetes Endocrinol. 2020;8:524-534.
Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: a systematic review [published correction appears in Lancet Neurol 2006 Feb;5(2):113]. Lancet Neurol. 2006;5:64-74.
Gudala K, Bansal D, Schifano F, Bhansali A. Diabetes mellitus and risk of dementia: a meta-analysis of prospective observational studies. J Diabetes Investig. 2013;4:640-650.
Smolina K, Wotton CJ, Goldacre MJ. Risk of dementia in patients hospitalised with type 1 and type 2 diabetes in England, 1998-2011: a retrospective national record linkage cohort study. Diabetologia. 2015;58:942-950.
Zhang J, Chen C, Hua S, et al. An updated meta-analysis of cohort studies: diabetes and risk of Alzheimer's disease. Diabetes Res Clin Pract. 2017;124:41-47.
Arnold SE, Arvanitakis Z, Macauley-Rambach SL, et al. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat Rev Neurol. 2018;14:168-181.
Biessels GJ, Nobili F, Teunissen CE, Simó R, Scheltens P. Understanding multifactorial brain changes in type 2 diabetes: a biomarker perspective. Lancet Neurol. 2020;19:699-710.
De Felice FG. Alzheimer's disease and insulin resistance: translating basic science into clinical applications. J Clin Invest. 2013;123:531-539.
Kellar D, Craft S. Brain insulin resistance in Alzheimer's disease and related disorders: mechanisms and therapeutic approaches. Lancet Neurol. 2020;19:758-766.
Banting FG, Best CH. The internal secretion of the pancreas. J Lab Clin Med. 1922;7:251-266.
Miles WR, Root HF. Psychologic tests applied in diabetic patients. Arch Internal Med. 1922;30:767-777.
Biessels GJ, Kappelle AC, Bravenboer B, Erkelens DW, Gispen WH. Cerebral function in diabetes mellitus. Diabetologia. 1994;37:643-650.
McCall AL. The impact of diabetes on the CNS. Diabetes. 1992;41:557-570.
Mooradian AD, Perryman K, Fitten J, Kavonian GD, Morley JE. Cortical function in elderly non-insulin dependent diabetic patients. Behavioral and electrophysiologic studies. Arch Intern Med. 1988;148:2369-2372.
Mooradian AD. Diabetic complications of the central nervous system. Endocr Rev. 1988;9:346-356.
Perlmuter LC, Hakami MK, Hodgson-Harrington C, et al. Decreased cognitive function in aging non-insulin-dependent diabetic patients. Am J Med. 1984;77:1043-1048.
Reaven GM, Thompson LW, Nahum D, Haskins E. Relationship between hyperglycemia and cognitive function in older NIDDM patients. Diabetes Care. 1990;13:16-21.
U'Ren RC, Riddle MC, Lezak MD, Bennington-Davis M. The mental efficiency of the elderly person with type II diabetes mellitus. J Am Geriatr Soc. 1990;38:505-510.
Attems J, Jellinger KA. The overlap between vascular disease and Alzheimer's disease-lessons from pathology. BMC Med. 2014;12:206.
Gladman JT, Corriveau RA, Debette S, et al. Vascular contributions to cognitive impairment and dementia: research consortia that focus on etiology and treatable targets to lessen the burden of dementia worldwide. Alzheimers Dement. 2019;5:789-796.
Zlokovic BV, Gottesman RF, Bernstein KE, et al. Vascular contributions to cognitive impairment and dementia (VCID): a report from the 2018 National Heart, Lung, and Blood Institute and National Institute of Neurological Disorders and Stroke Workshop. Alzheimer's & Dementia. 2020;16:1714-1733.
Skoog I. Risk factors for vascular dementia: a review. Dementia. 1994;5:137-144.
Mortel KF, Wood S, Pavol MA, Meyer JS, Rexer JL. Analysis of familial and individual risk factors among patients with ischemic vascular dementia and Alzheimer's disease. Angiology. 1993;44:599-605.
Yoshitake T, Kiyohara Y, Kato I, et al. Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study. Neurology. 1995;45:1161-1168.
Ott A, Stolk RP, Hofman A, van Harskamp F, Grobbee DE, Breteler MM. Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia. 1996;39:1392-1397.
Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology. 1999;53:1937-1942.
Chatterjee S, Peters SA, Woodward M, et al. Type 2 diabetes as a risk factor for dementia in women compared with men: a pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia. Diabetes Care. 2016;39:300-307.
Fontbonne A, Berr C, Ducimetière P, Alpérovitch A. Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. Diabetes Care. 2001;24:366-370.
Logroscino G, Kang JH, Grodstein F. Prospective study of type 2 diabetes and cognitive decline in women aged 70-81 years. BMJ. 2004;328:548.
Wu JH, Haan MN, Liang J, Ghosh D, Gonzalez HM, Herman WH. Impact of diabetes on cognitive function among older Latinos: a population-based cohort study. J Clin Epidemiol. 2003;56:686-693.
Yaffe K, Blackwell T, Kanaya AM, Davidowitz N, Barrett-Connor E, Krueger K. Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology. 2004;63:658-663.
Yaffe K, Falvey C, Hamilton N, et al. Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia. Arch Neurol. 2012;69:1170-1175.
Ravona-Springer R, Moshier E, Schmeidler J, et al. Changes in glycemic control are associated with changes in cognition in non-diabetic elderly. J Alzheimers Dis. 2012;30:299-309.
Frölich L, Blum-Degen D, Bernstein HG, et al. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm. 1998;105:423-438.
Hoyer S. Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis. J Neural Transm. 1998;105:415-422.
Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine. J Alzheimers Dis. 2005;8:247-268.
Steen E, Terry BM, Rivera EJ, 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;7:63-80.
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 [published correction appears in Proc Natl Acad Sci USA 2009;106:7678]. Proc Natl Acad Sci U S A. 2009;106:1971-1976.
Moloney AM, Griffin RJ, Timmons S, O'Connor R, Ravid R, O'Neill C. 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;31:224-243.
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;122:1316-1338.
Bomfim TR, Forny-Germano L, Sathler LB, et al. An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease- associated Aβ oligomers. J Clin Invest. 2012;122:1339-1353.
Li X, Alafuzoff I, Soininen H, Winblad B, Pei JJ. Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain. FEBS J. 2005;272:4211-4220.
Pei JJ, Khatoon S, An WL, et al. Role of protein kinase B in Alzheimer's neurofibrillary pathology. Acta Neuropathol. 2003;105:381-392.
Rickle A, Bogdanovic N, Volkman I, Winblad B, Ravid R, Cowburn RF. Akt activity in Alzheimer's disease and other neurodegenerative disorders. NeuroReport. 2004;15:955-959.
Kalmijn S, Foley D, White L, et al. Metabolic cardiovascular syndrome and risk of dementia in Japanese-American elderly men. The Honolulu-Asia aging study. Arterioscler Thromb Vasc Biol. 2000;20:2255-2260.
Kivipelto M, Ngandu T, Fratiglioni L, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol. 2005;62:1556-1560.
Melo HM, Seixas da Silva GDS, Sant'Ana MR, et al. Palmitate is increased in the cerebrospinal fluid of humans with obesity and induces memory impairment in mice via pro-inflammatory TNF-α. Cell Rep. 2020;30:2180-2194.e8.
Biddinger SB, Kahn CR. From mice to men: insights into the insulin resistance syndromes. Annu Rev Physiol. 2006;68:123-158.
Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011;29:415-445.
Hotamisligil GS, Spiegelman BM. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes. 1994;43:1271-1278.
Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860-867.
Hotamisligil GS. Molecular mechanisms of insulin resistance and the role of the adipocyte. Int J Obes Relat Metab Disord. 2000;24(Suppl 4):S23-S27.
Peraldi P, Spiegelman B. TNF-alpha and insulin resistance: summary and future prospects. Mol Cell Biochem. 1998;182:169-175.
Hotamisligil GS. Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes. Diabetes. 2005;54(Suppl 2):S73-S78.
Hotamisligil GS. The role of TNFα and TNF receptors in obesity and insulin resistance. J Intern Med. 1999;245:621-625.
Aguzzi A, Barres BA, Bennett ML. Microglia: scapegoat, saboteur, or something else? Science. 2013;339:156-161.
De Felice FG, Ferreira ST. Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease. Diabetes. 2014;63:2262-2272.
Ferreira ST, Clarke JR, Bomfim TR, De Felice FG. Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer's disease. Alzheimers Dement. 2014;10(1 Suppl):S76-S83.
Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol. 2015a;14:388-405.
Heneka MT, Golenbock DT, Latz E. Innate immunity in Alzheimer's disease. Nat Immunol. 2015b;16:229-236.
Selles MC, Oliveira MM, Ferreira ST. Brain inflammation connects cognitive and non-cognitive symptoms in Alzheimer's disease. J Alzheimers Dis. 2018;64(s1):S313-S327.
Ferreira ST, Klein WL. The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's disease. Neurobiol Learn Mem. 2011;96:529-543.
Ferreira ST, Lourenco MV, Oliveira MM, De Felice FG. Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer's disease. Front Cell Neurosci. 2015;9:191.
Ferreira ST, Vieira MN, De Felice FG. Soluble protein oligomers as emerging toxins in Alzheimer's and other amyloid diseases. IUBMB Life. 2007;59:332-345.
Li S, Selkoe DJ. A mechanistic hypothesis for the impairment of synaptic plasticity by soluble Aβ oligomers from Alzheimer's brain. J Neurochem. 2020;154:583-597.
Forny-Germano L, Lyra e Silva NM, Batista AF, et al. Alzheimer's disease-like pathology induced by amyloid-β oligomers in nonhuman primates. J Neurosci. 2014;34:13629-13643.
Kincheski GC, Valentim IS, Clarke JR, et al. Chronic sleep restriction promotes brain inflammation and synapse loss, and potentiates memory impairment induced by amyloid-β oligomers in mice. Brain Behav Immun. 2017;64:140-151.
Ledo JH, Azevedo EP, Beckman D, et al. Cross talk between brain innate immunity and serotonin signaling underlies depressive-like behavior induced by Alzheimer's amyloid-β oligomers in mice. J Neurosci. 2016;36:12106-12116.
Ledo JH, Azevedo EP, Clarke JR, et al. Amyloid-β oligomers link depressive-like behavior and cognitive deficits in mice [published correction appears in Mol Psychiatry 2020 Sep 2]. Mol Psychiatry. 2013;18:1053-1054.
Lourenco MV, Clarke JR, Frozza RL, et al. TNF-α mediates PKR-dependent memory impairment and brain IRS-1 inhibition induced by Alzheimer’s β-amyloid oligomers in mice and monkeys. Cell Metab. 2013;18:831-843.
Brosseron F, Krauthausen M, Kummer M, Heneka MT. Body fluid cytokine levels in mild cognitive impairment and Alzheimer's disease: a comparative overview. Mol Neurobiol. 2014;50:534-544.
Tarkowski E, Tullberg M, Fredman P, Wikkelsö C. Correlation between intrathecal sulfatide and TNF-alpha levels in patients with vascular dementia. Dement Geriatr Cogn Disord. 2003;15:207-211.
Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010;140:900-917.
De Felice FG, Lourenco MV, Ferreira ST. How does brain insulin resistance develop in Alzheimer's disease? Alzheimers Dement. 2014;10(1 Suppl):S26-S32.
Ferreira LSS, Fernandes CS, Vieira MNN, De Felice FG. Insulin resistance in Alzheimer's disease. Front Neurosci. 2018;12:830.
Lourenco MV, Ferreira ST, De Felice FG. Neuronal stress signaling and eIF2α phosphorylation as molecular links between Alzheimer's disease and diabetes. Prog Neurogibol. 2015;129:37-57.
Lyra E, Silva NM, Gonçalves RA, et al. Understanding the link between insulin resistance and Alzheimer's disease: insights from animal models. Exp Neurol. 2019;316:1-11.
Franceschi C, Bonafè M, Valensin S, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann NY Acad Sci. 2000;908:244-254.
Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14:576-590.
Ferrario CR, Reagan LP. Insulin-mediated synaptic plasticity in the CNS: anatomical, functional and temporal contexts. Neuropharmacology. 2018;136:182-191.
Gralle M. The neuronal insulin receptor in its environment. J Neurochem. 2017;140:359-367.
Decker H, Jürgensen S, Adrover MF, et al. N-methyl-D-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-β peptide oligomers. J Neurochem. 2010;115:1520-1529.
Batista AF, Bodart-Santos V, De Felice FG, Ferreira ST. Neuroprotective actions of glucagon-like peptide-1 (GLP-1) analogues in Alzheimer's and Parkinson's diseases. CNS Drugs. 2019;33:209-223.
Hölscher C. Brain insulin resistance: role in neurodegenerative disease and potential for targeting. Expert Opin Investig Drugs. 2020;29:333-348.
Batista AF, Forny-Germano L, Clarke JR, et al. The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer's disease. J Pathol. 2018;245:85-100.
McClean PL, Parthsarathy V, Faivre E, Hölscher C. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease. J Neurosci. 2011;31:6587-6594.
Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci. 2002;5:514-516.
Hanson LR, Frey WH. Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease. BMC Neurosci. 2008;9(Suppl 3):S5.
Owens DR. New horizons-alternative routes for insulin therapy. Nat Rev Drug Discov. 2002;1:529-540.
Reger MA, Craft S. Intranasal insulin administration: a method for dissociating central and peripheral effects of insulin. Drugs Today (Barc). 2006;42:729-739.
Thorne RG, Pronk GJ, Padmanabhan V, Frey WH 2nd. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience. 2004;127:481-496.
Benedict C, Hallschmid M, Hatke A, et al. Intranasal insulin improves memory in humans. Psychoneuroendocrinology. 2004;29:1326-1334.
Benedict C, Hallschmid M, Schultes B, Born J, Kern W. Intranasal insulin to improve memory function in humans. Neuroendocrinology. 2007;86:136-142.
Benedict C, Kern W, Schultes B, Born J, Hallschmid M. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. J Clin Endocrinol Metab. 2008;93:1339-1344.
Krug R, Benedict C, Born J, Hallschmid M. Comparable sensitivity of postmenopausal and young women to the effects of intranasal insulin on food intake and working memory. J Clin Endocrinol Metab. 2010;95:E468-E472.
Freiherr J, Hallschmid M, Frey WH 2nd, et al. Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence. CNS Drugs. 2013;27:505-514.
Craft S, Baker LD, Montine TJ, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012;69:29-38.
Reger MA, Watson GS, Frey WH 2nd, et al. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging. 2006;27:451-458.
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;13:323-331.
Reger MA, Watson GS, Green PS, et al. Intranasal insulin improves cognition and modulates beta-amyloid in early AD [published correction appears in Neurology 2008 Sep 9;71:866]. Neurology. 2008;70:440-448.
Yamazaki Y, Zhao N, Caulfield TR, Liu CC, Bu G. Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. Nat Rev Neurol. 2019;15:501-518.
Schiöth HB, Craft S, Brooks SJ, Frey WH 2nd, Benedict C. Brain insulin signaling and Alzheimer's disease: current evidence and future directions. Mol Neurobiol. 2012;46:4-10.
Craft S, Claxton A, Baker LD, et al. Effects of regular and long-acting insulin on cognition and Alzheimer's disease biomarkers: a pilot clinical trial. J Alzheimers Dis. 2017;57:1325-1334.
Craft S, Raman R, Chow TW, et al. Safety, efficacy, and feasibility of intranasal insulin for the treatment of mild cognitive impairment and Alzheimer disease dementia: a randomized clinical trial [published online ahead of print, 2020 Jun 22]. JAMA Neurol. 2020;77:1-11.
Craft S, Raman R, Chow TW, et al. “Open Label Extension Results from a Phase II/III Trial of Intranasal Insulin”. Alzheimer's Dementia. 15(S1489).
Jack CR Jr, Holtzman DM. Biomarker modeling of Alzheimer's disease. Neuron. 2013;80:1347-1358.
Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:280-292.
Gubbi S, Quipildor GF, Barzilai N, Huffman DM, Milman S. 40 Years of IGF1: IGF1: the Jekyll and Hyde of the aging brain. J Mol Endocrinol. 2018;61:T171-T185.
Wrigley S, Arafa D, Tropea D. Insulin-like growth factor 1: at the crossroads of brain development and aging. Front Cell Neurosci. 2017;11:14.
Aleman A, Verhaar HJ, De Haan EH, et al. Insulin-like growth factor-I and cognitive function in healthy older men. J Clin Endocrinol Metab. 1999;84:471-475.
Chao XL, Jiang SZ, Xiong JW, et al. The association between serum insulin-like growth factor 1 and cognitive impairments in patients with schizophrenia. Psychiatry Res. 2020;285:112731.
Doi T, Shimada H, Makizako H, et al. Association of insulin-like growth factor-1 with mild cognitive impairment and slow gait speed. Neurobiol Aging. 2015;36:942-947.
Paolisso G, Barbagallo M. Hypertension, diabetes mellitus, and insulin resistance: the role of intracellular magnesium. Am J Hypertens. 1997;10:346-355.
Rollero A, Murialdo G, Fonzi S, et al. Relationship between cognitive function, growth hormone and insulin-like growth factor I plasma levels in aged subjects. Neuropsychobiology. 1998;38:73-79.
Sanders JL, Ding V, Arnold AM, et al. Do changes in circulating biomarkers track with each other and with functional changes in older adults? J Gerontol A Biol Sci Med Sci. 2014;69:174-181.
Frater J, Lie D, Bartlett P, McGrath JJ. Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: a review. Ageing Res Rev. 2018;42:14-27.
Newman AB, Sanders JL, Kizer JR, et al. Trajectories of function and biomarkers with age: the CHS All Stars Study. Int J Epidemiol. 2016;45:1135-1145.
Papadakis MA, Grady D, Tierney MJ, Black D, Wells L, Grunfeld C. Insulin-like growth factor 1 and functional status in healthy older men. J Am Geriatr Soc. 1995;43:1350-1355.
Perice L, Barzilai N, Verghese J, et al. Lower circulating insulin-like growth factor-I is associated with better cognition in females with exceptional longevity without compromise to muscle mass and function. Aging. 2016;8:2414-2424.
Sonntag WE, Bennett SA, Khan AS, et al. Age and insulin-like growth factor-1 modulate N-methyl-D-aspartate receptor subtype expression in rats. Brain Res Bull. 2000;51:331-338.
Sonntag WE, Lynch C, Thornton P, Khan A, Bennett S, Ingram R. The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing. J Anat. 2000;197:575-585.
Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Sonntag WE, Riddle DR. Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience. 2001;107:603-613.
Lynch CD, Lyons D, Khan A, Bennett SA, Sonntag WE. Insulin-like growth factor-1 selectively increases glucose utilization in brains of aged animals. Endocrinology. 2001;142:506-509.
Fernandez AM, Hernandez E, Guerrero-Gomez D, Miranda-Vizuete A, Torres Aleman I. A network of insulin peptides regulate glucose uptake by astrocytes: potential new druggable targets for brain hypometabolism. Neuropharmacology. 2018;136:216-222.
Markowska AL, Mooney M, Sonntag WE. Insulin-like growth factor-1 ameliorates age-related behavioral deficits. Neuroscience. 1998;87:559-569.
Mustafa A, Lannfelt L, Lilius L, Islam A, Winblad B, Adem A. Decreased plasma insulin-like growth factor-I level in familial Alzheimer's disease patients carrying the Swedish APP 670/671 mutation. Dement Geriatr Cogn Disord. 1999;10:446-451.
Vidal JS, Hanon O, Funalot B, et al. Low serum insulin-like growth factor-I predicts cognitive decline in Alzheimer's disease. J Alzheimers Dis. 2016;52:641-649.
Zegarra-Valdivia JA, Santi A, Fernández de Sevilla ME, Nuñez A, Torres AI. Serum insulin-like growth factor I deficiency associates to Alzheimer's disease co-morbidities. J Alzheimers Dis. 2019;69:979-987.
Ostrowski PP, Barszczyk A, Forstenpointner J, Zheng W, Feng ZP. Meta-analysis of serum insulin-like growth factor 1 in Alzheimer's disease. PLoS One. 2016;11:e0155733.
Carro E, Trejo JL, Gomez-Isla T, LeRoith D, Torres-Aleman I. Serum insulin-like growth factor I regulates brain amyloid-beta levels. Nat Med. 2002;8:1390-1397.
Carro E, Trejo JL, Spuch C, Bohl D, Heard JM, Torres-Aleman I. Blockade of the insulin-like growth factor I receptor in the choroid plexus originates Alzheimer's-like neuropathology in rodents: new cues into the human disease? Neurobiol Aging. 2006a;27:1618-1631.
Furigo IC, Melo HM, Lyra e Silva NM, et al. Brain STAT5 signaling modulates learning and memory formation. Brain Struct Funct. 2018;223:2229-2241.
Poirier R, Fernandez AM, Torres-Aleman I, Metzger F. Early brain amyloidosis in APP/PS1 mice with serum insulin-like growth factor-I deficiency. Neurosci Lett. 2012;509:101-104.
Carro E, Trejo JL, Gerber A, et al. Therapeutic actions of insulin-like growth factor I on APP/PS2 mice with severe brain amyloidosis. Neurobiol Aging. 2006;27:1250-1257.
George C, Gontier G, Lacube P, François JC, Holzenberger M, Aïd S. The Alzheimer's disease transcriptome mimics the neuroprotective signature of IGF-1 receptor-deficient neurons. Brain. 2017;140:2012-2027.
Gontier G, George C, Chaker Z, Holzenberger M, Aïd S. Blocking IGF signaling in adult neurons alleviates Alzheimer's disease pathology through amyloid-β clearance. J Neurosci. 2015;35:11500-11513.
Puig KL, Kulas JA, Franklin W, et al. The Ames dwarf mutation attenuates Alzheimer's disease phenotype of APP/PS1 mice. Neurobiol Aging. 2016;40:22-40.
Clemmons DR. Role of IGF binding proteins in regulating metabolism. Trends Endocrinol Metab. 2016;27:375-391.
Lewitt MS, Boyd GW. The role of insulin-like growth factors and insulin-like growth factor-binding proteins in the nervous system. Biochem Insights. 2019;12:1178626419842176.
Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease [published correction appears in Nat Rev Mol Cell Biol. 2020 Jan 31]. Nat Rev Mol Cell Biol. 2020;21:183-203.
Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol. 2009;10:307-318.
Tahmasebi S, Khoutorsky A, Mathews MB, Sonenberg N. Translation deregulation in human disease. Nat Rev Mol Cell Biol. 2018;19:791-807.
Pelletier J, Sonenberg N. The organizing principles of eukaryotic ribosome recruitment. Annu Rev Biochem. 2019;88:307-335.
Richter JD, Sonenberg N. Regulation of cap-dependent translation by eIF4E inhibitory proteins. Nature. 2005;433:477-480.
Sonenberg N, Dever TE. Eukaryotic translation initiation factors and regulators. Curr Opin Struct Biol. 2003;13:56-63.
Banko JL, Merhav M, Stern E, Sonenberg N, Rosenblum K, Klann E. Behavioral alterations in mice lacking the translation repressor 4E-BP2. Neurobiol Learn Mem. 2007;87:248-256.
Banko JL, Poulin F, Hou L, DeMaria CT, Sonenberg N, Klann E. The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus. J Neurosci. 2005;25:9581-9590.
Ran I, Gkogkas CG, Vasuta C, et al. Selective regulation of GluA subunit synthesis and AMPA receptor-mediated synaptic function and plasticity by the translation repressor 4E-BP2 in hippocampal pyramidal cells. J Neurosci. 2013;33:1872-1886.
Ma YQ, Wu DK, Liu JK. mTOR and tau phosphorylated proteins in the hippocampal tissue of rats with type 2 diabetes and Alzheimer's disease. Mol Med Rep. 2013;7:623-627.
Oliveira MM, Lourenco MV, Longo F, et al. Correction of eIF2-dependent defects in brain protein synthesis, synaptic plasticity and memory in mouse models of Alzheimer’s disease. Sci Signal. 2021;14:eabc5429.
Perluigi M, Di Domenico F, Butterfield DA. mTOR signaling in aging and neurodegeneration: at the crossroad between metabolism dysfunction and impairment of autophagy. Neurobiol Dis. 2015;84:39-49.
Talboom JS, Velazquez R, Oddo S. The mammalian target of rapamycin at the crossroad between cognitive aging and Alzheimer's disease. NPJ Aging Mech Dis. 2015;1:15008.
Di Domenico F, Barone E, Perluigi M, Butterfield DA. The triangle of death in Alzheimer’s disease brain: the aberrant cross-talk among energy metabolism, mammalian target of rapamycin signaling, and protein homeostasis revealed by redox proteomics. Antioxid Redox Signal. 2017;26:364-387.
Sun Y-X, Ji X, Mao X, et al. Differential activation of mTOR complex 1 signaling in human brain with mild to severe Alzheimer’s disease. J Alzheimers Dis. 2014;38:437-444.
Tramutola A, Triplett JC, Di Domenico F, et al. Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD. J Neurochem. 2015;133:739-749.
Darnell JC, Klann E. The translation of translational control by FMRP: therapeutic targets for FXS. Nat Neurosci. 2013;16:1530-1536.
Santini E, Klann E. Reciprocal signaling between translational control pathways and synaptic proteins in autism spectrum disorders. Sci Signal. 2014;7:re10.
Pitt J, Wilcox KC, Tortelli V, et al. Neuroprotective astrocyte-derived insulin/insulin-like growth factor 1 stimulates endocytic processing and extracellular release of neuron-bound Aβ oligomers. Mol Biol Cell. 2017;28:2623-2636.
Selles MC, Fortuna JTS, Zappa-Villar MF, et al. Adenovirus-mediated transduction of insulin-like growth factor 1 protects hippocampal neurons from the toxicity of Aβ oligomers and prevents memory loss in an Alzheimer mouse model. Mol Neurobiol. 2020;57:1473-1483.
Hereñú CB, Cristina C, Rimoldi OJ, et al. Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction. Gene Ther. 2007;14:237-245.
Pardo J, Uriarte M, Cónsole GM, et al. Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats. Eur J Neurosci. 2016;44:2120-2128.
Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013;17:819-837.
Varndell IM, Bishop AE, Sikri KL, Uttenthal LO, Bloom SR, Polak JM. Localization of glucagon-like peptide (GLP) immunoreactants in human gut and pancreas using light and electron microscopic immunocytochemistry. J Histochem Cytochem. 1985;33:1080-1086.
Andersen A, Lund A, Knop FK, Vilsbøll T. Glucagon-like peptide 1 in health and disease. Nat Rev Endocrinol. 2018;14:390-403.
Larsen PJ, Tang-Christensen M, Holst JJ, Orskov C. Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem. Neuroscience. 1997;77:257-270.
Llewellyn-Smith IJ, Gnanamanickam GJ, Reimann F, Gribble FM, Trapp S. Preproglucagon (PPG) neurons innervate neurochemically identified autonomic neurons in the mouse brainstem. Neuroscience. 2013;229:130-143.
Llewellyn-Smith IJ, Reimann F, Gribble FM, Trapp S. Preproglucagon neurons project widely to autonomic control areas in the mouse brain. Neuroscience. 2011;180:111-121.
Vrang N, Hansen M, Larsen PJ, Tang-Christensen M. Characterization of brainstem preproglucagon projections to the paraventricular and dorsomedial hypothalamic nuclei. Brain Res. 2007;1149:118-126.
Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2-terminus in type II diabetic patients and in healthy subjects. Diabetes. 1995;44:1126-1131.
Deacon CF. Metabolism of GIP and the contribution of GIP to the glucose-lowering properties of DPP-4 inhibitors. Peptides. 2020;125:170196.
Bhavsar S, Mudaliar S, Cherrington A. Evolution of exenatide as a diabetes therapeutic. Curr Diabetes Rev. 2013;9:161-193.
Liu XY, Wang LX, Chen Z, Liu LB. Liraglutide prevents beta-amyloid-induced neurotoxicity in SH-SY5Y cells via a PI3K-dependent signaling pathway. Neurol Res. 2016;38:313-319.
McClean PL, Hölscher C. Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease. Neuropharmacology. 2014;76:57-67.
Sharma MK, Jalewa J, Hölscher C. Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to methylglyoxal stress. J Neurochem. 2014;128:459-471.
Chen S, Sun J, Zhao G, et al. Liraglutide improves water maze learning and memory performance while reduces hyperphosphorylation of tau and neurofilaments in APP/PS1/Tau triple transgenic mice. Neurochem Res. 2017;42:2326-2335.
Hansen HH, Fabricius K, Barkholt P, et al. The GLP-1 receptor agonist liraglutide improves memory function and increases hippocampal CA1 neuronal numbers in a senescence-accelerated mouse model of Alzheimer's disease. J Alzheimers Dis. 2015;46:877-888.
McClean PL, Jalewa J, Hölscher C. Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice. Behav Brain Res. 2015;293:96-106.
Qi L, Ke L, Liu X, et al. Subcutaneous administration of liraglutide ameliorates learning and memory impairment by modulating tau hyperphosphorylation via the glycogen synthase kinase-3β pathway in an amyloid β protein induced Alzheimer disease mouse model. Eur J Pharmacol. 2016;783:23-32.
Hansen HH, Fabricius K, Barkholt P, et al. Long-term treatment with liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has no effect on β-amyloid plaque load in two transgenic APP/PS1 mouse models of Alzheimer's disease. PLoS One. 2016;11:e0158205.
Cai HY, Yang JT, Wang ZJ, et al. Lixisenatide reduces amyloid plaques, neurofibrillary tangles and neuroinflammation in an APP/PS1/tau mouse model of Alzheimer's disease. Biochem Biophys Res Commun. 2018;495:1034-1040.
Athauda D, Maclagan K, Skene SS, et al. Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390:1664-1675.
Athauda D, Foltynie T. Protective effects of the GLP-1 mimetic exendin-4 in Parkinson's disease. Neuropharmacology. 2018;136:260-270.
Aviles-Olmos I, Dickson J, Kefalopoulou Z, et al. Exenatide and the treatment of patients with Parkinson's disease. J Clin Invest. 2013;123:2730-2736.
Aviles-Olmos I, Dickson J, Kefalopoulou Z, et al. Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson's disease. J Parkinsons Dis. 2014;4:337-344.
Mullins RJ, Mustapic M, Chia CW, et al. A pilot study of exenatide actions in Alzheimer's disease. Curr Alzheimer Res. 2019;16:741-752.
Gejl M, Brock B, Egefjord L, Vang K, Rungby J, Gjedde A. Blood-brain glucose transfer in Alzheimer's disease: effect of GLP-1 analog treatment. Sci Rep. 2017;7:17490.
Gejl M, Gjedde A, Egefjord L, et al. In Alzheimer's disease, 6-month treatment with GLP-1 analog prevents decline of brain glucose metabolism: randomized, placebo-controlled, double-blind clinical trial. Front Aging Neurosci. 2016;8:108.
Femminella GD, Frangou E, Love SB, et al. Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer's disease: study protocol for a randomised controlled trial (ELAD study) [published correction appears in Trials 2020 Jul 19;21(1):660]. Trials. 2019;20:191.
Grant Information :
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro; Instituto Nacional de Ciência e Tecnologia de Neurociência Translacional; Conselho Nacional de Desenvolvimento Científico e Tecnológico
Contributed Indexing :
Keywords: Aβ oligomers; dementia; incretins; insulin resistance
Entry Date(s) :
Date Created: 20210319 Latest Revision: 20210419
Update Code :
Czasopismo naukowe
Although the brain was once considered an insulin-independent organ, insulin signalling is now recognised as being central to neuronal health and to the function of synapses and brain circuits. Defective brain insulin signalling, as well as related signalling by insulin-like growth factor 1 (IGF-1), is associated with neurological disorders, including Alzheimer's disease, suggesting that cognitive impairment could be related to a state of brain insulin resistance. Here, I briefly review key epidemiological/clinical evidence of the association between diabetes, cognitive decline and AD, as well as findings of reduced components of insulin signalling in AD brains, which led to the initial suggestion that AD could be a type of brain diabetes. Particular attention is given to recent studies illuminating mechanisms leading to neuronal insulin resistance as a key driver of cognitive impairment in AD. Evidence of impaired IGF-1 signalling in AD is also examined. Finally, we discuss potentials and possible limitations of recent and on-going therapeutic approaches based on our increased understanding of the roles of brain signalling by insulin, IGF-1 and glucagon-like peptide 1 in AD.
(© 2021 British Society for Neuroendocrinology.)

Ta witryna wykorzystuje pliki cookies do przechowywania informacji na Twoim komputerze. Pliki cookies stosujemy w celu świadczenia usług na najwyższym poziomie, w tym w sposób dostosowany do indywidualnych potrzeb. Korzystanie z witryny bez zmiany ustawień dotyczących cookies oznacza, że będą one zamieszczane w Twoim komputerze. W każdym momencie możesz dokonać zmiany ustawień dotyczących cookies