Neuroprotection by the multitarget iron chelator M30 on age-related alterations in mice

Mechanisms of Ageing and Development

Volumn 133, Issue 5, 2012, Pages 267-274

  Kupershmidt, Lana ^a   Amit, Tamar ^a   Bar Am, Orit ^a   Youdim, Moussa B H ^a   Weinreb, Orly ^a  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

Author keywords

Amyloid plaques; Ageing; Iron chelator; Monoamine oxidase inhibitor; Neuroprotection

Indexed keywords

2 METHYL 5 (3,4,5 TRIMETHOXYBENZAMIDO)DECAHYDROISOQUINOLINE; 5 (N METHYL N PROPARGYLAMINOMETHYL) 8 HYDROXYQUINOLONE; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME A; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME B; AMYLOID BETA PROTEIN; IRON CHELATING AGENT; UNCLASSIFIED DRUG;

AGED; AMYLOID PLAQUE; ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; COGNITIVE DEFECT; CONTROLLED STUDY; DRUG MECHANISM; ENZYME ACTIVITY; ENZYME INHIBITION; LONG TERM MEMORY; MALE; MEMORY CONSOLIDATION; MEMORY DISORDER; MENTAL TASK; MOUSE; NERVE DEGENERATION; NEUROPROTECTION; NEUROPSYCHIATRY; NONHUMAN; OPEN FIELD BEHAVIOR; PRIORITY JOURNAL; SHORT TERM MEMORY; TASK PERFORMANCE;

AGING; AMYLOID BETA-PEPTIDES; ANIMALS; CEREBRUM; CHELATING AGENTS; COGNITION DISORDERS; HYDROXYQUINOLINES; IRON; MALE; MICE; MICE, INBRED C57BL; MONOAMINE OXIDASE INHIBITORS; NEUROPROTECTIVE AGENTS; NEUROPSYCHOLOGICAL TESTS;

MUS; PARKINSONIA;

EID: 84861235044     PISSN: 00476374     EISSN: 18726216     Source Type: Journal    
DOI: 10.1016/j.mad.2012.03.001     Document Type: Article

References (67)

1. Amit T., Avramovich-Tirosh Y., Youdim M.B., Mandel S. Targeting multiple Alzheimer's disease etiologies with multimodal neuroprotective and neurorestorative iron chelators. FASEB J. 2008, 22:1296-1305.
2. Avramovich-Tirosh Y., Amit T., Bar-Am O., Zheng H., Fridkin M., Youdim M.B. Therapeutic targets and potential of the novel brain- permeable multifunctional iron chelator-monoamine oxidase inhibitor drug, M-30, for the treatment of Alzheimer's disease. J. Neurochem. 2007, 100:490-502.
3. Avramovich-Tirosh Y., Reznichenko L., Mit T., Zheng H., Fridkin M., Weinreb O., Mandel S., Youdim M.B. Neurorescue activity, APP regulation and amyloid-beta peptide reduction by novel multi-functional brain permeable iron-chelating-antioxidants, M-30 and green tea polyphenol, EGCG. Curr. Alzheimer Res. 2007, 4:403-411.
4. Avramovich-Tirosh Y., Amit T., Bar-Am O., Weinreb O., Youdim M.B. Physiological and pathological aspects of Abeta in iron homeostasis via 5'UTR in the APP mRNA and the therapeutic use of iron-chelators. BMC Neurosci. 2008, 9(Suppl. 2):S2.
5. Avramovich-Tirosh Y., Bar-Am O., Amit T., Youdim M.B., 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. 2010, 7:300-306.
6. Banks W.A., Farr S.A., Morley J.E., Wolf K.M., Geylis V., Steinitz M. Anti-amyloid beta protein antibody passage across the blood-brain barrier in the SAMP8 mouse model of Alzheimer's disease: an age-related selective uptake with reversal of learning impairment. Exp. Neurol. 2007, 206:248-256.
7. Bar-Am O., Amit T., Weinreb O., Youdim M.B., Mandel S. Propargylamine containing compounds as modulators of proteolytic cleavage of amyloid-beta protein precursor: involvement of MAPK and PKC activation. J. Alzheimers Dis. 2010, 21:361-371.
8. Bartzokis G., Mintz J., Sultzer D., Marx P., Herzberg J.S., Phelan C.K., Marder S.R. In vivo MR evaluation of age-related increases in brain iron. AJNR Am. J. Neuroradiol. 1994, 15:1129-1138.
9. Bartzokis G., Cummings J.L., Markham C.H., Marmarelis P.Z., Treciokas L.J., Tishler T.A., Marder S.R., Mintz J. MRI evaluation of brain iron in earlier- and later-onset Parkinson's disease and normal subjects. Magn. Reson. Imaging 1999, 17:213-222.
10. Benkovic S.A., Connor J.R. Ferritin, transferrin, and iron in selected regions of the adult and aged rat brain. J. Comp. Neurol. 1993, 338:97-113.
11. Berr C., Balansard B., Arnaud J., Roussel A.M., Alperovitch A. Cognitive decline is associated with systemic oxidative stress: the EVA study. Etude du Vieillissement Arteriel. J. Am. Geriatr. Soc. 2000, 48:1285-1291.
12. Binda C., Hubalek F., Li M., Herzig Y., Sterling J., Edmondson D.E., Mattevi A. Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class. J. Med. Chem. 2004, 47:1767-1774.
13. Bortolato M., Chen K., Shih J.C. Monoamine oxidase inactivation: from pathophysiology to therapeutics. Adv. Drug Deliv. Rev. 2008, 60:1527-1533.
14. Carrillo M.C., Minami C., Kitani K., Maruyama W., Ohashi K., Yamamoto T., Naoi M., Kanai S., Youdim M.B. Enhancing effect of rasagiline on superoxide dismutase and catalase activities in the dopaminergic system in the rat. Life Sci. 2000, 67:577-585.
15. Chintala S., Novak E.K., Spernyak J.A., Mazurchuk R., Torres G., Patel S., Busch K., Meeder B.A., Horowitz J.M., Vaughan M.M., Swank R.T. The Vps33a gene regulates behavior and cerebellar Purkinje cell number. Brain Res. 2009, 1266:18-28.
16. de Lima M.N., Laranja D.C., Caldana F., Bromberg E., Roesler R., Schroder N. Reversal of age-related deficits in object recognition memory in rats with l-deprenyl. Exp. Gerontol. 2005, 40:506-511.
17. de Lima M.N., Dias C.P., Torres J.P., Dornelles A., Garcia V.A., Scalco F.S., Guimaraes M.R., Petry R.C., Bromberg E., Constantino L., Budni P., Dal-Pizzol F., Schroder N. Reversion of age-related recognition memory impairment by iron chelation in rats. Neurobiol. Aging 2008, 29:1052-1059.
18. Deacon R.M., Cholerton L.L., Talbot K., Nair-Roberts R.G., Sanderson D.J., Romberg C., Koros E., Bornemann K.D., Rawlins J.N. Age-dependent and -independent behavioral deficits in Tg2576 mice. Behav. Brain Res. 2008, 189:126-138.
19. Droge W., Schipper H.M. Oxidative stress and aberrant signaling in aging and cognitive decline. Aging Cell 2007, 6:361-370.
20. Filali M., Lalonde R., Rivest S. Cognitive and non-cognitive behaviors in an APPswe/PS1 bigenic model of Alzheimer's disease. Genes Brain Behav. 2009, 8:143-148.
21. Floor E. Iron as a vulnerability factor in nigrostriatal degeneration in aging and Parkinson's disease. Cell Mol. Biol. (Noisy-le-grand) 2000, 46:709-720.
22. Gal S., Zheng H., Fridkin M., Youdim M.B. Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases. In vivo selective brain monoamine oxidase inhibition and prevention of MPTP-induced striatal dopamine depletion. J. Neurochem. 2005, 95:79-88.
23. Gal S., Zheng H., Fridkin M., Youdim M.B. Restoration of nigrostriatal dopamine neurons in post-MPTP treatment by the novel multifunctional brain-permeable iron chelator-monoamine oxidase inhibitor drug, M30. Neurotox. Res. 2010, 17:15-27.
24. Harman A.W., Adamson G.M., Shaw S.G. Protection from oxidative damage in mouse liver cells. Toxicol. Lett. 1992, 64-65:581-587.
25. Head E., Moffat K., Das P., Sarsoza F., Poon W.W., Landsberg G., Cotman C.W., Murphy M.P. Beta-amyloid deposition and tau phosphorylation in clinically characterized aged cats. Neurobiol. Aging 2005, 26:749-763.
26. Irwin I., Finnegan K.T., Delanney L.E., Di Monte D., Langston J.W. The relationships between aging, monoamine oxidase, striatal dopamine and the effects of MPTP in C57BL/6 mice: a critical reassessment. Brain Res. 1992, 572:224-231.
27. Kitani K., Miyasaka K., Kanai S., Carrillo M.C., Ivy G.O. Upregulation of antioxidant enzyme activities by deprenyl. Implications for life span extension. Ann. N.Y. Acad. Sci. 1996, 786:391-409.
28. Kitani K., Kanai S., Ivy G.O., Carrillo M.C. Assessing the effects of deprenyl on longevity and antioxidant defenses in different animal models. Ann. N.Y. Acad. Sci. 1998, 854:291-306.
29. Kitani K., Kanai S., Ivy G.O., Carrillo M.C. Pharmacological modifications of endogenous antioxidant enzymes with special reference to the effects of deprenyl: a possible antioxidant strategy. Mech. Ageing Dev. 1999, 111:211-221.
30. Knoll J. (-)Deprenyl (selegiline), a catecholaminergic activity enhancer (CAE) substance acting in the brain. Pharmacol. Toxicol. 1998, 82:57-66.
31. Kumar M.J., Andersen J.K. Perspectives on MAO-B in aging and neurological disease: where do we go from here?. Mol. Neurobiol. 2004, 30:77-89.
32. Kupershmidt L., Weinreb O., Amit T., Mandel S., Carri M.T., Youdim M.B. Neuroprotective and neuritogenic activities of novel multimodal iron-chelating drugs in motor-neuron-like NSC-34 cells and transgenic mouse model of amyotrophic lateral sclerosis. FASEB J. 2009, 23:3766-3779.
33. Kupershmidt L., Weinreb O., Amit T., Mandel S., Bar-Am O., Youdim M.B. Novel molecular targets of the neuroprotective/neurorescue multimodal iron chelating drug M30 in the mouse brain. Neuroscience 2011, 189:345-358.
34. Kupershmidt L, Amit T, Bar Am O, Youdim MB, Weinreb O., 2012. The novel multi-target iron chelating-radical scavenging compound M30 possesses beneficial effects on major hallmarks of Alzheimer's disease. Antioxid Redox Signal. doi:10.1089/ars.2011.4279.
35. Li Y., Zhou W., Tong Y., He G., Song W. Control of APP processing and Abeta generation level by BACE1 enzymatic activity and transcription. FASEB J. 2006, 20:285-292.
36. Lu T., Pan Y., Kao S.Y., Li C., Kohane I., Chan J., Yankner B.A. Gene regulation and DNA damage in the ageing human brain. Nature 2004, 429:883-891.
37. Ludolph A.C., Bendotti C., Blaugrund E., Hengerer B., Loffler J.P., Martin J., Meininger V., Meyer T., Moussaoui S., Robberecht W., Scott S., Silani V., Van Den Berg L.H. Guidelines for the preclinical in vivo evaluation of pharmacological active drugs for ALS/MND: report on the 142nd ENMC international workshop. Amyotroph. Lateral Scler. 2007, 8:217-223.
38. Payton S., Cahill C.M., Randall J.D., Gullans S.R., Rogers J.T. Drug discovery targeted to the Alzheimer's APP mRNA 5'-untranslated region: the action of paroxetine and dimercaptopropanol. J. Mol. Neurosci. 2003, 20:267-275.
39. Perkins A.J., Hendrie H.C., Callahan C.M., Gao S., Unverzagt F.W., Xu Y., Hall K.S., Hui S.L. Association of antioxidants with memory in a multiethnic elderly sample using the Third National Health and Nutrition Examination Survey. Am. J. Epidemiol. 1999, 150:37-44.
40. Poon H.F., Calabrese V., Calvani M., Butterfield D.A. Proteomics analyses of specific protein oxidation and protein expression in aged rat brain and its modulation by l-acetylcarnitine: insights into the mechanisms of action of this proposed therapeutic agent for CNS disorders associated with oxidative stress. Antioxid. Redox Signal 2006, 8:381-394.
41. Preston J.E. Ageing choroid plexus-cerebrospinal fluid system. Microsc. Res. Tech. 2001, 52:31-37.
42. Reddy P.H., Manczak M., Mao P., Calkins M.J., Reddy A.P., Shirendeb U. Amyloid-beta and mitochondria in aging and Alzheimer's disease: implications for synaptic damage and cognitive decline. J. Alzheimers Dis. 2010, 20(Suppl. 2):S499-S512.
43. Reznichenko L., Amit T., Zheng H., Avramovich-Tirosh Y., Youdim M.B., Weinreb O., Mandel S. Reduction of iron-regulated amyloid precursor protein and beta-amyloid peptide by (-)-epigallocatechin-3-gallate in cell cultures: implications for iron chelation in Alzheimer's disease. J. Neurochem. 2006, 97:527-536.
44. Riederer P., Danielczyk W., Grunblatt E. Monoamine oxidase-B inhibition in Alzheimer's disease. Neurotoxicology 2004, 25:271-277.
45. Rinaldi P., Polidori M.C., Metastasio A., Mariani E., Mattioli P., Cherubini A., Catani M., Cecchetti R., Senin U., Mecocci P. Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer's disease. Neurobiol. Aging 2003, 24:915-919.
46. Rogers J.T., Lahiri D.K. Metal and inflammatory targets for Alzheimer's disease. Curr. Drug Targets 2004, 5:535-551.
47. Rogers D.C., Peters J., Martin J.E., Ball S., Nicholson S.J., Witherden A.S., Hafezparast M., Latcham J., Robinson T.L., Quilter C.A., Fisher E.M. SHIRPA, a protocol for behavioral assessment: validation for longitudinal study of neurological dysfunction in mice. Neurosci. Lett. 2001, 306:89-92.
48. Rogers J.T., Randall J.D., Cahill C.M., Eder P.S., Huang X., Gunshin H., Leiter L., McPhee J., Sarang S.S., Utsuki T., Greig N.H., Lahiri D.K., Tanzi R.E., Bush A.I., Giordano T., Gullans S.R. An iron-responsive element type II in the 5'-untranslated region of the Alzheimer's amyloid precursor protein transcript. J. Biol. Chem. 2002, 277:45518-45528.
49. Saura J., Richards J.G., Mahy N. Differential age-related changes of MAO-A and MAO-B in mouse brain and peripheral organs. Neurobiol. Aging 1994, 15:399-408.
50. Sayre L.M., Perry G., Atwood C.S., Smith M.A. The role of metals in neurodegenerative diseases. Cell Mol. Biol. (Noisy-le-grand) 2000, 46:731-741.
51. Shemyakov S.E. Monoamine oxidase activity, lipid peroxidation, and morphological changes in human hypothalamus during aging. Bull. Exp. Biol. Med. 2001, 131:586-588.
52. Simola N., Bustamante D., Pinna A., Pontis S., Morales P., Morelli M., Herrera-Marschitz M. Acute perinatal asphyxia impairs non-spatial memory and alters motor coordination in adult male rats. Exp. Brain Res. (Experimentelle Hirnforschung) 2008, 185:595-601.
53. Suh J.H., Moreau R., Heath S.H., Hagen T.M. Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep. 2005, 10:52-60.
54. Tipton K.F., McCrodden J.M., Kalir A.S., Youdim M.B. Inhibition of rat liver monoamine oxidase by alpha-methyl- and N-propargyl-amine derivatives. Biochem. Pharmacol. 1982, 31:1251-1255.
55. Vassar R., Bennett B.D., Babu-Khan S., Kahn S., Mendiaz E.A., Denis P., Teplow D.B., Ross S., Amarante P., Loeloff R., Luo Y., Fisher S., Fuller J., Edenson S., Lile J., Jarosinski M.A., Biere A.L., Curran E., Burgess T., Louis J.C., Collins F., Treanor J., Rogers G., Citron M. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999, 286:735-741.
56. Vaucher E., Aumont N., Pearson D., Rowe W., Poirier J., Kar S. Amyloid beta peptide levels and its effects on hippocampal acetylcholine release in aged, cognitively-impaired and -unimpaired rats. J. Chem. Neuroanat. 2001, 21:323-329.
57. Vymazal J., Righini A., Brooks R.A., Canesi M., Mariani C., Leonardi M., Pezzoli G. T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content. Radiology 1999, 211:489-495.
58. Weinreb O., Drigues N., Sagi Y., Reznick A.Z., Amit T., Youdim M.B. The application of proteomics and genomics to the study of age-related neurodegeneration and neuroprotection. Antioxid. Redox Signal 2007, 9:169-179.
59. Yankner B.A., Lu T., Loerch P. The aging brain. Annu. Rev. Pathol. 2008, 3:41-66.
60. Yogev-Falach M., Amit T., Bar-Am O., Weinstock M., Youdim M.B. Involvement of MAP kinase in the regulation of amyloid precursor protein processing by novel cholinesterase inhibitors derived from rasagiline. FASEB J. 2002, 16:1674-1676.
61. Yokel R.A. Blood-brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration. J. Alzheimers. Dis. 2006, 10:223-253.
62. Youdim M.B., Buccafusco J.J. Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders. Trends Pharmacol. Sci. 2005, 26:27-35.
63. Zecca L., Youdim M.B., Riederer P., Connor J.R., Crichton R.R. Iron, brain ageing and neurodegenerative disorders. Nat. Rev. Neurosci. 2004, 5:863-873.
64. Zheng H., Gal S., Weiner L.M., Bar-Am O., Warshawsky A., Fridkin M., Youdim M.B. Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition. J. Neurochem. 2005, 95:68-78.
65. Zheng H., Weiner L.M., Bar-Am O., Epsztejn S., Cabantchik Z.I., Warshawsky A., Youdim M.B., Fridkin M. 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. 2005, 13:773-783.
66. Zhu W., Xie W., Pan T., Xu P., Fridkin M., Zheng H., Jankovic J., Youdim M.B., Le W. Prevention and restoration of lactacystin-induced nigrostriatal dopamine neuron degeneration by novel brain-permeable iron chelators. FASEB J. 2007, 21:3835-3844.
67. Zou L., Yang R., Zhang P., Dai Y. The enhancement of amyloid precursor protein and beta-site amyloid cleavage enzyme 1 interaction: amyloid-beta production with aging. Int. J. Mol. Med. 2010, 25:401-407.