The novel multi-target iron chelator, M30 modulates HIF-1α-related glycolytic genes and insulin signaling pathway in the frontal cortex of APP/PS1 Alzheimer's disease mice

Current Alzheimer Research

Volumn 11, Issue 2, 2014, Pages 119-127

  Mechlovich, Danit ^a   Amit, Tamar ^a   Bar Am, Orit ^a   Mandel, Silvia ^a   Youdim, Moussa B H ^a   Weinreb, Orly ^a  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

Author keywords

Alzheimer's disease; Hypoxia inducible factor 1 ; Insulin signaling pathway; Iron chelation; Neuroprotection

Indexed keywords

2 METHYL 5 (3,4,5 TRIMETHOXYBENZAMIDO)DECAHYDROISOQUINOLINE; 5 (N METHYL N PROPARGYLAMINOMETHYL) 8 HYDROXYQUINOLINE; AMYLOID PRECURSOR PROTEIN; ENOLASE; FRUCTOSE BISPHOSPHATE ALDOLASE; GLUCOSE; GLUCOSE TRANSPORTER 1; GLYCOGEN SYNTHASE KINASE 3BETA; GLYCOLYTIC ENZYME; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INSULIN; INSULIN RECEPTOR; IRON CHELATING AGENT; LIVER PROTEIN; NEUROPROTECTIVE AGENT; PRESENILIN 1; UNCLASSIFIED DRUG; 5-(N-METHYL-N-PROPARGYLAMINOMETHYL)-8-HYDROXYQUINOLINE; HIF1A PROTEIN, MOUSE; PRESENILIN 1, MOUSE; QUINOLINOL DERIVATIVE; SLC2A1 PROTEIN, MOUSE;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BRAIN LEVEL; CONTROLLED STUDY; DOSE RESPONSE; DRUG TARGETING; ENZYME PHOSPHORYLATION; EXPERIMENTAL NEUROLOGIC DISEASE; FRONTAL CORTEX; GLUCOSE BLOOD LEVEL; GLUCOSE TOLERANCE; GLUCOSE TOLERANCE TEST; GLYCOLYSIS; INSULIN BRAIN LEVEL; LIVER LEVEL; LONG TERM CARE; MALE; MODULATION; MOUSE; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; ANIMAL; BIOSYNTHESIS; DRUG DELIVERY SYSTEM; DRUG EFFECTS; FRONTAL LOBE; GENETICS; METABOLISM; PHYSIOLOGY; PROCEDURES;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; DRUG DELIVERY SYSTEMS; FRONTAL LOBE; GLUCOSE TRANSPORTER TYPE 1; GLYCOLYSIS; HYDROXYQUINOLINES; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; INSULIN; IRON CHELATING AGENTS; MALE; MICE; PRESENILIN-1; SIGNAL TRANSDUCTION;

EID: 84897457767     PISSN: 15672050     EISSN: 18755828     Source Type: Journal    
DOI: 10.2174/1567205010666131212112529     Document Type: Article

References (66)

1. Ahmad W. Overlapped metabolic and therapeutic links between Alzheimer and diabetes. Mol Neurobiol 47: 399-424 (2013).
2. Correia SC, Santos RX, Carvalho C, Cardoso S, Candeias E, Santos MS, et al. Insulin signaling, glucose metabolism and mitochondria: major players in Alzheimer's disease and diabetes interrelation. Brain Res 1441: 64-78 (2012).
3. Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D, Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology 50: 164-168 (1998).
4. Craft S, Asthana S, Cook DG, Baker LD, Cherrier M, Purganan K, et al. Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer's disease: interactions with apolipoprotein E genotype. Psychoneuroendocrinology 28: 809-822 (2003).
5. 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 8: 247-268 (2005).
6. 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 Alzheimer's disease--is this type 3 diabetes? J Alzheimers Dis 7: 63-80 (2005).
7. Cao D, Lu H, Lewis TL, Li L. Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J Biol Chem 282: 36275-36282 (2007).
8. Ho L, Qin W, Pompl PN, Xiang Z, Wang J, Zhao Z, et al. Dietinduced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease. FASEB J 18: 902-904 (2004).
9. Takeda S, Sato N, Uchio-Yamada K, Sawada K, Kunieda T, Takeuchi D, et al. Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes. Proc Natl Acad Sci USA 107: 7036-7041 (2010).
10. Pedersen WA, McMillan PJ, Kulstad JJ, Leverenz JB, Craft S, Haynatzki GR. Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice. Exp Neurol 199: 265-273 (2006).
11. McClean PL, Parthsarathy V, Faivre E, Holscher C. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease. J Neurosci 31: 6587-6594 (2011).
12. Li J, Deng J, Sheng W, Zuo Z. Metformin attenuates Alzheimer's disease-like neuropathology in obese, leptin-resistant mice. Pharmacol Biochem Behav 101: 564-574 (2012).
13. Pintana H, Apaijai N, Pratchayasakul W, Chattipakorn N, Chattipakorn SC. Effects of metformin on learning and memory behaviors and brain mitochondrial functions in high fat diet induced insulin resistant rats. Life Sci 91: 409-414 (2012).
14. Dominguez RO, Marschoff ER, Gonzalez SE, Repetto MG, Serra JA. Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients. Diabetes Res Clin Pract 98: 68-74 (2012).
15. Beeri MS, Schmeidler J, Silverman JM, Gandy S, Wysocki M, Hannigan CM, et al. Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology. Neurology 71: 750-757 (2008).
16. Guo X, Geng M, Du G. Glucose transporter 1, distribution in the brain and in neural disorders: its relationship with transport of neuroactive drugs through the blood-brain barrier. Biochem Genet 43: 175-187(2005).
17. Hooijmans CR, Graven C, Dederen PJ, Tanila H, van Groen T, Kiliaan AJ. Amyloid beta deposition is related to decreased glucose transporter-1 levels and hippocampal atrophy in brains of aged APP/PS1 mice. Brain Res 1181: 93-103(2007).
18. Zheng H, Weiner LM, Bar-Am O, Epsztejn S, Cabantchik ZI, Warshawsky A, et al. Design, synthesis, and evaluation of novel bifunctional iron-chelators as potential agents for neuroprotection in Alzheimer's, Parkinson's, and other neurodegenerative diseases. Bioorg Med Chem 13: 773-783 (2005).
19. Kupershmidt L, Amit T, Bar-Am O, Youdim MB, Weinreb O. Neuroprotection by the multitarget iron chelator M30 on agerelated alterations in mice. Mech Ageing Dev 133: 267-274 (2012).
20. Kupershmidt L, Amit T, Bar-Am O, Youdim MB, Weinreb O. The novel multi-target iron chelating-radical scavenging compound M30 possesses beneficial effects on major hallmarks of Alzheimer's disease. Antioxid Redox Signal 17: 860-877 (2012).
21. Weinreb O, Amit T, Mandel S, Kupershmidt L, Youdim MB. Neuroprotective multifunctional iron chelators: from redoxsensitive process to novel therapeutic opportunities. Antioxid Redox Signal 13: 919-949 (2010).
22. Siddiq A, Ayoub IA, Chavez JC, Aminova L, Shah S, LaManna JC, et al. Hypoxia-inducible factor prolyl 4-hydroxylase inhibition. A target for neuroprotection in the central nervous system. J Biol Chem 280: 41732-41743 (2005).
23. Li YX, Ding SJ, Xiao L, Guo W, Zhan Q. Desferoxamine preconditioning protects against cerebral ischemia in rats by inducing expressions of hypoxia inducible factor 1 alpha and erythropoietin. Neurosci Bull 24: 89-95 (2008).
24. Hamrick SE, McQuillen PS, Jiang X, Mu D, Madan A, Ferriero DM. A role for hypoxia-inducible factor-1alpha in desferoxamine neuroprotection. Neurosci Lett 379: 96-100 (2005).
25. Zaman K, Ryu H, Hall D, O'Donovan K, Lin KI, Miller MP, et al. Protection from oxidative stress-induced apoptosis in cortical neuronal cultures by iron chelators is associated with enhanced DNA binding of hypoxia-inducible factor-1 and ATF-1/CREB and increased expression of glycolytic enzymes, p21(waf1/cip1), and erythropoietin. J Neurosci 19: 9821-9830 (1999).
26. Kupershmidt L, Weinreb O, Amit T, Mandel S, Bar-Am O, Youdim MB. Novel molecular targets of the neuroprotective/ neurorescue multimodal iron chelating drug M30 in the mouse brain. Neuroscience 189: 345-358 (2011).
27. Cooksey RC, Jones D, Gabrielsen S, Huang J, Simcox JA, Luo B, et al. Dietary iron restriction or iron chelation protects from diabetes and loss of beta-cell function in the obese (ob/ob lep-/-) mouse. Am J Physiol Endocrinol Metab 298: E1236-1243(2010).
28. Fernandez-Real JM, Penarroja G, Castro A, Garcia-Bragado F, Hernandez-Aguado I, Ricart W. Blood letting in high-ferritin type 2 diabetes: effects on insulin sensitivity and beta-cell function. Diabetes 51: 1000-1004 (2002).
29. Forouhi NG, Harding AH, Allison M, Sandhu MS, Welch A, Luben R, et al. Elevated serum ferritin levels predict new-onset type 2 diabetes: results from the EPIC-Norfolk prospective study. Diabetologia 50: 949-956 (2007).
30. Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB. Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA 291: 711-717 (2004).
31. Wilson JG, Lindquist JH, Grambow SC, Crook ED, Maher JF. Potential role of increased iron stores in diabetes. Am J Med Sci 325: 332-339 (2003).
32. Zheng H, Gal S, Weiner LM, Bar-Am O, Warshawsky A, Fridkin M, et al. Novel multifunctional neuroprotective iron chelatormonoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition. J Neurochem 95: 68-78 (2005).
33. Filali M, Lalonde R, Rivest S. Cognitive and non-cognitive behaviors in an APPswe/PS1 bigenic model of Alzheimer's disease. Genes Brain Behav 8: 143-148 (2009).
34. Zhu W, Xie W, Pan T, Xu P, Fridkin M, Zheng H, et al. Prevention and restoration of lactacystin-induced nigrostriatal dopamine neuron degeneration by novel brain-permeable iron chelators. FASEB J 21: 3835-3844 (2007).
35. Weinreb O, Mandel S, Youdim MB. cDNA gene expression profile homology of antioxidants and their antiapoptotic and proapoptotic activities in human neuroblastoma cells. FASEB J 17: 935-937 (2003).
36. Rajpathak SN, Crandall JP, Wylie-Rosett J, Kabat GC, Rohan TE, Hu FB. The role of iron in type 2 diabetes in humans. Biochim Biophys Acta 1790: 671-681(2009).
37. Forde JE, Dale TC. Glycogen synthase kinase 3: a key regulator of cellular fate. Cell Mol Life Sci 64: 1930-1944 (2007).
38. Semenza GL. Expression of hypoxia-inducible factor 1: mechanisms and consequences. Biochem Pharmacol 59: 47-53 (2000).
39. Semenza GL. Hypoxia, clonal selection, and the role of HIF-1 in tumor progression. Crit Rev Biochem Mol Biol 35: 71-103 (2000).
40. Craft S. Insulin resistance and Alzheimer's disease pathogenesis: potential mechanisms and implications for treatment. Curr Alzheimer Res 4: 147-152(2007).
41. Neumann KF, Rojo L, Navarrete LP, Farias G, Reyes P, Maccioni RB. Insulin resistance and Alzheimer's disease: molecular links & clinical implications. Curr Alzheimer Res 5: 438-447(2008).
42. Frolich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S, et al. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm 105: 423-438 (1998).
43. Leal MC, Fernandez Gamba A, Morelli L, Castano EM. Cerebral proteolysis of amiloid-b peptide: relevance of insulin-degrading enzyme in Alzheimer's disease. Medicina (B Aires) 69: 466-472 (2009).
44. Watson GS, Craft S. Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer's disease. Eur J Pharmacol 490: 97-113 (2004).
45. Cardoso S, Correia S, Santos RX, Carvalho C, Santos MS, Oliveira CR, et al. Insulin is a two-edged knife on the brain. J Alzheimers Dis 18: 483-507 (2009).
46. Hernandez F, Avila J. The role of glycogen synthase kinase 3 in the early stages of Alzheimers' disease. FEBS Lett 582: 3848-3854 (2008).
47. Balaraman Y, Limaye AR, Levey AI, Srinivasan S Glycogen synthase kinase 3beta and Alzheimer's disease: pathophysiological and therapeutic significance. Cell Mol Life Sci 63: 1226-1235 (2006).
48. Hooper C, Killick R, Lovestone S. The GSK3 hypothesis of Alzheimer's disease. J Neurochem 104: 1433-1439 (2008).
49. Talbot K, Wang HY, Kazi H, Han LY, Bakshi KP, Stucky A, 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 122: 1316-1338 (2012).
50. Avramovich-Tirosh Y, Bar-Am O, Amit T, Youdim MB, Weinreb O. Up-regulation of hypoxia-inducible factor (HIF)-1alpha and HIF-target genes in cortical neurons by the novel multifunctional iron chelator anti-Alzheimer drug, M30. Curr Alzheimer Res 7: 300-306 (2010).
51. Heidenreich KA, Zahniser NR, Berhanu P, Brandenburg D, Olefsky JM. Structural differences between insulin receptors in the brain and peripheral target tissues. J Biol Chem 258: 8527-8530 (1983).
52. Lowe WL, Jr., Boyd FT, Clarke DW, Raizada MK, Hart C, LeRoith D. Development of brain insulin receptors: structural and functional studies of insulin receptors from whole brain and primary cell cultures. Endocrinology 119: 25-35 (1986).
53. Biessels GJ, Kamal A, Ramakers GM, Urban IJ, Spruijt BM, Erkelens DW, et al. Place learning and hippocampal synaptic plasticity in streptozotocin-induced diabetic rats. Diabetes 45: 1259-1266 (1996).
54. Heras-Sandoval D, Ferrera P, Arias C. Amyloid-beta protein modulates insulin signaling in presynaptic terminals. Neurochem Res 37: 1879-1885 (2012).
55. Qiu WQ, Folstein MF. Insulin, insulin-degrading enzyme and amyloid-beta peptide in Alzheimer's disease: review and hypothesis. Neurobiol Aging 27: 190-198 (2006).
56. Cook DG, Leverenz JB, McMillan PJ, Kulstad JJ, Ericksen S, Roth RA, et al. Reduced hippocampal insulin-degrading enzyme in lateonset Alzheimer's disease is associated with the apolipoprotein Eepsilon4 allele. Am J Pathol 162: 313-319 (2003).
57. Zhao L, Teter B, Morihara T, Lim GP, Ambegaokar SS, Ubeda OJ, et al. Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention. J Neurosci 24: 11120-11126 (2004).
58. Liu Y, Liu F, Iqbal K, Grundke-Iqbal I, Gong CX. Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease. FEBS Lett 582: 359-364 (2008).
59. Chen C, Pore N, Behrooz A, Ismail-Beigi F, Maity A. Regulation of glut1 mRNA by hypoxia-inducible factor-1. Interaction between H-ras and hypoxia. J Biol Chem 276: 9519-9525 (2001).
60. Hayashi M, Sakata M, Takeda T, Yamamoto T, Okamoto Y, Sawada K, et al. Induction of glucose transporter 1 expression through hypoxia-inducible factor 1alpha under hypoxic conditions in trophoblast-derived cells. J Endocrinol 183: 145-154(2004).
61. Maxwell PH, Dachs GU, Gleadle JM, Nicholls LG, Harris AL, Stratford IJ, et al. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA 94: 8104-8109 (1997).
62. Zelzer E, Levy Y, Kahana C, Shilo BZ, Rubinstein M, Cohen B. Insulin induces transcription of target genes through the hypoxiainducible factor HIF-1alpha/ARNT. EMBO J 17: 5085-5094 (1998).
63. Pollak Y, Mechlovich D, Amit T, Bar-Am O, Manov I, Mandel SA, et al. Effects of novel neuroprotective and neurorestorative multifunctional drugs on iron chelation and glucose metabolism. J Neural Transm 120: 37-48 (2013).
64. Fargion S, Dongiovanni P, Guzzo A, Colombo S, Valenti L, Fracanzani AL. Iron and insulin resistance. Aliment Pharmacol Ther 22(2): 61-63(2005).
65. Dongiovanni P, Valenti L, Ludovica Fracanzani A, Gatti S, Cairo G, Fargion S. Iron depletion by deferoxamine up-regulates glucose uptake and insulin signaling in hepatoma cells and in rat liver. Am J Pathol 172: 738-747(2008).
66. Fernandez-Real JM, Lopez-Bermejo A, Ricart W. Iron stores, blood donation, and insulin sensitivity and secretion. Clin Chem 51: 1201-1205 (2005).