Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases

Mechanisms of Ageing and Development

Volumn 126, Issue 2, 2005, Pages 317-326

  Youdim, Moussa B H ^a   Fridkin, Mati ^b   Zheng, Hailin ^b  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^b WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

Alzheimer's disease; Amyloid precursor protein; Bcl 2 family proteins; Cholinesterase; Inhibitors; Iron chelators; Ladostigil (TV3326); MAPkinase; Monoamine oxidase; Neuroprotection; Parkinson's disease; PKC; Propargylamines; Rasagiline

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; ACETIC ACID DERIVATIVE; AMINE; ANTIDEPRESSANT AGENT; ANTIPARKINSON AGENT; CARBAMIC ACID DERIVATIVE; CHOLINESTERASE; CHOLINESTERASE INHIBITOR; FERROUS GLUCONATE; IRON; IRON CHELATING AGENT; LADOSTIGIL; MONOAMINE OXIDASE A INHIBITOR; MONOAMINE OXIDASE B INHIBITOR; NEUROPROTECTIVE AGENT; NORADRENALIN; PROPARGYLAMINE; PROTEIN BAD; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; RASAGILINE; SEROTONIN; TYRAMINE; UNCLASSIFIED DRUG; VK 28;

AGING; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; BRAIN MATURATION; BRAIN REGION; CONFERENCE PAPER; DEGENERATIVE DISEASE; DEMENTIA; DISEASE ASSOCIATION; DRUG ACTIVITY; DRUG EFFICACY; DRUG INDICATION; DRUG POTENTIATION; HLA SYSTEM; HUMAN; HUNTINGTON CHOREA; IN VITRO STUDY; IN VIVO STUDY; LEWY BODY; MITOCHONDRION; MOLECULAR MECHANICS; NEUROPROTECTION; NONHUMAN; NORADRENALIN BRAIN LEVEL; OXIDATIVE STRESS; PARKINSON DISEASE; PARKINSONISM; PERMEABILITY; PRESSOR RESPONSE; PRIORITY JOURNAL; PROTEIN FAMILY; SEROTONIN BRAIN LEVEL; SPATIAL MEMORY;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; BRAIN; CHELATING AGENTS; CHOLINESTERASE INHIBITORS; CHOLINESTERASES; CULTURE MEDIA, SERUM-FREE; DEMENTIA; DOPAMINE; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; INDANS; IRON; LEWY BODIES; MAP KINASE SIGNALING SYSTEM; MODELS, CHEMICAL; MONOAMINE OXIDASE; MONOAMINE OXIDASE INHIBITORS; NEURODEGENERATIVE DISEASES; NEURONS; PIPERAZINES; PROTEIN KINASE C; PROTO-ONCOGENE PROTEINS C-BCL-2; QUINOLINES;

GYMNOMYZA SAMOENSIS;

EID: 11144316146     PISSN: 00476374     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mad.2004.08.023     Document Type: Conference Paper

References (65)

1. D. Aarsland, C. Ballard, I. McKeith, R.H. Perry, and J.P. Larsen Dementia with Lewy bodies treated with rivastigmine: effects on cognition, neuropsychiatric symptoms, and sleep J. Neuropsychiatry Clin. Neurosci. 13 2001 374 379
2. S. Abu-Raya, E. Blaugrund, V. Trembovler, E. Shilderman-Bloch, E. Shohami, and P. Lazarovici Rasagiline, a monoamine oxidase-B inhibitor, protects NGF-differentiated PC12 cells against oxygen-glucose deprivation J. Neurosci. Res. 58 1999 456 463
3. E. Arnaiz, V. Jelic, O. Almkvist, L.O. Wahlund, B. Winblad, S. Valind, and A. Nordberg Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment Neuroreport 26 2001 851 855
4. O. Bar Am, T. Amit, and M.B.H. Youdim Contrasting neuroprotective and neurotoxic actions of respective metabolites of antiparkinson drugs rasagiline and selegiline Neurosci. Lett. 355 2004 169 172
5. O. Bar Am, M. Yogev-Falach, T. Amit, Y. Sagi, and M.B.H. Youdim Regulation of amyloid precursor protein and protein kinase C functional machinery by the anti-Parkinson drug, rasagiline and its derivatives, in vivo J. Neurochem. 89 2004 1119 1125
6. D.B. Ben Shachar, N. Kahana, V. Kampel, A. Warshawsky, and M.B. Youdim Neuroprotection by a novel brain permeable iron chelator, VK-28, against 6-hydroxydopamine lesion in rats Neuropharmacology 46 2004 254 263
7. D. Ben Shachar, G. Eshel, J.P. Finberg, and M.B. Youdim The iron chelator desferrioxamine (Desferal) retards 6-hydroxydopamine-induced degeneration of nigrostriatal dopamine neurons J. Neurochem. 56 1991 1441 1444
8. F. Borsini, and A. Meli Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology 94 1988 147 160
9. M.C. Carrillo, C. Minami, K. Kiting, W. Maruyama, K. Hash, T. Yamamoto, M. Naomi, S. Kanai, and M.B. Youdim Enhancing effect of rasagiline on superoxide dismutase and catalase activities in the dopaminergic system in the rat Life Sci. 67 2000 577 585
10. D.S. Cassarino, and J.P. Bennett An evaluation of the role of mitochondria in neurodegenerative diseases: mitochondrial mutations and oxidative pathology, protective nuclear responses, and cell death in neurodegeneration Brain Res. Rev. 29 1999 1 25
11. D.E. Edmondson, C. Binda, and A. Mattevi The FAD binding sites of human monoamine oxidases A and B Neurotoxicology 25 2004 63 72
12. J.P. Finberg, I. Lamensdorf, M. Weinstock, M. Schwartz, and M.B. Youdim Pharmacology of rasagiline (N-propargyl-1R-aminoindan) Adv. Neurol. 80 1999 495 499
13. J.P. Finberg, M. Tenne, and M.B. Youdim Tyramine antagonistic properties of AGN 1135, an irreversible inhibitor of monoamine oxidase type B Br. J. Pharmacol. 73 1981 65 74
14. J.P. Finberg, and M.B. Youdim Modification of blood pressure and nictitating membrane response to sympathetic amines by selective monoamine oxidase inhibitors, types A and B, in the cat Br. J. Pharmacol. 85 1985 541 546
15. E. Giacobini Selective inhibitors of butyrylcholinesterase: a valid alternative for therapy of Alzheimer's disease? Drugs Aging 18 2001 891 898
16. Parkinson Study Group A controlled clinical trial of rasagiline in early Parkinson's disease: the TEMPO Study Arch. Neurol. 59 2002 1937 1943
17. Parkinson Study Group A controlled randomized, delayed-start study of rasagiline in early Parkinson's disease Arch. Neurol. 61 2004 561 567
18. E. Grunblatt, S. Mandel, G. Maor, and M.B.H. Youdim Effects of R-apomorphine and S-apomorphine on MPTP-induced nigro-striatal dopamine neuronal loss J. Neurochem. 76 2001 1 12
19. W. Gsell, R. Conrad, M. Hickethier, E. Sofic,. L. Frolich,. I. Wichart, K. Jellinger, G. Moll, G. Ransmayr, and H. Beckmann Decreased catalase activity but unchanged superoxide dismutase activity in brains of patients with dementia of Alzheimer type J. Neurochem. 64 1995 1216 1223
20. R.E. Heikkila, R.C. Duvoisin, J.P. Finberg, and M.B. Youdim Prevention of MPTP-induced neurotoxicity by AGN-1133 and AGN-1135, selective inhibitors of monoamine oxidase-B Eur. J. Pharmacol. 116 1985 313 317
21. W. Huang, Y. Chen, E. Shohami, and M. Weinstock Neuroprotective effect of rasagiline, a selective MAO-B inhibitor, against closed head injury in the mouse Eur. J. Pharmacol. 366 1999 127 135
22. M.W. Jann Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer's disease Pharmacotherapy 20 2000 1 12
23. A. Kalir, A. Sabbagh, and M.B.H. Youdim Selective acetylenic 'suicide' and reversible inhibitors of monoamine oxidase types A and B Br. J. Pharmacol. 73 1981 55 64
24. W. Maruyama, T. Yamamoto, K. Kitani, M.C. Carrillo, M. Youdim, and M. Naoi Mechanism underlying anti-apoptotic activity of a (-)deprenyl-related propargylamine, rasagiline Mech. Ageing Dev. 116 2000 181 191
25. W. Maruyama, Y. Akao, M.B.H. Youdim, and M. Naoi Neurotoxins induce apoptosis in dopamine neurons: protection by N-propargylamine-1(R)- and (S)-aminoindan, rasagiline and TV1022 J. Neural Transm. Suppl. 60 2000 171 186
26. W. Maruyama, M.B. Youdim, and M. Naoi Antiapoptotic properties of rasagiline, N-propargylamine-1(R)-aminoindan, and its optical (S)-isomer, TV1022 Ann. N. Y. Acad. Sci. 939 2001 320 329
27. W. Maruyama, Y. Akao, M.B. Youdim, B.A. Davis, and M. Naoi Transfection-enforced Bcl-2 over expression and an anti-Parkinson drug, rasagiline, prevent nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol J. Neurochem. 78 2001 727 735
28. W. Maruyama, M. Weinstock, M.B. Youdim, M. Nagai, and M. Naoi Anti-apoptotic action of anti-Alzheimer drug, TV3326 [(N-propargyl)-(3R)- aminoindan-5-yl]-ethyl methyl carbamate, a novel cholinesterase-monoamine oxidase inhibitor Neurosci. Lett. 341 2003 233 236
29. I.G. McKeith, D. Galasko, K. Kosaka, E.K. Perry, D.W. Dickson, L.A. Hansen, D.P. Salmon, J. Lowe, S.S. Mirra, E.J. Byrne, G. Lennox, N.P. Quinn, J.A. Edwardson, P.G. Ince, C. Bergeron, A. Burns, B.L. Miller, S. Lovestone, D. Collerton, E.N. Jansen, C. Ballard, R.A. de Vos, G.K. Wilcock, K.A. Jellinger, and R.H. Perry Consensus guidelines for the clinical and pathological diagnosis of dementia with Lewy bodies (DLB). Report of the consortium on DLB international workshop Neurology 47 1996 1113 1124
30. I. McKeith, J. Mintzer, D. Aarsland, D. Burn, H. Chiu, J. Cohen-Mansfield, D. Dickson, B. Dubois, J.E. Duda, H. Feldman, S. Gauthier, G. Halliday, B. Lawlor, C. Lippa, O.L. Lopez, J. Carlos Machado, J. O'Brien, J. Playfer, and W. Reid International Psychogeriatric Association Expert Meeting on DLB. Dementia with Lewy bodies Lancet Neurol. 3 2004 19 28
31. R. Moretti, P. Torre, R.M. Antonello, and G. Cazzato Rivastigmine in subcortical vascular dementia: a comparison trial on efficacy and tolerability for 12 months follow-up Eur. Neurol. 8 2001 361 362
32. E.M. Mutisya, A.C. Bowling, and M.F. Beal Cortical cytochrome oxidase activity is reduced in Alzheimer's disease J. Neurochem. 63 1994 2179 2184
33. M. Naol, and W. Maruyama N-methyl(R)salsolinol, a dopamine neurotoxin, in Parkinson's disease Adv. Neurol. 80 1999 259 264
34. S.C. Newman The prevalence of depression in Alzheimer's disease and vascular dementia in a population sample J. Affect. Disord. 52 1999 169 176
35. A.M. Palmer, G.C. Stratman, A.W. Procter, and D.M. Bowen Possible neurotransmitter basis of behavioral changes in Alzheimer's disease Ann. Neurol. 23 1988 616 620
36. W.D. Parker Jr., S.J. Boyson, and J.K. Parks Abnormalities of the electron transport chain in idiopathic Parkinson's disease Ann. Neurol. 26 1989 719 723
37. R.H. Perry, D. Irving, G. Blessed, A. Fairbairn, and E.K. Perry Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly J. Neurol. Sci. 95 1991 119 139
38. R.D. Porsolt, A. Bertin, N. Blavet, M. Deniel, and M. Jalfre Immobility induced by forced swimming in rats: effects of agents which modify central catecholamine and serotonin activity Eur. J. Pharmacol. 57 1979 201 210
39. Y. Sagi, M. Weinstock, and M.B.H. Youdim Attenuation of MPTP-induced dopaminergic neurotoxicity by TV3326, a cholinesterase-monoamine oxidase inhibitor J. Neurochem. 86 2003 290 297
40. J. Saura, J.M. Luque, A.M. Cesura, M. Da Prada, V. Chan-Palay, G. Huber, J. Loffler, and J.G. Richards Increased monoamine oxidase B activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative radioautography Neuroscience 62 1994 15 30
41. I.A. Simpson, K.R. Chundu, T. Davies-Hill, W.G. Honer, and P. Davies Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease Ann. Neurol. 35 1994 546 551
42. W. Slikker, M.B. Youdim, G.C. Palmer, E. Hall, C. Williams, and B. Trembly The future of neuroprotection Ann. N. Y. Acad. Sci. 890 1999 529 533
43. Z. Speiser, R. Levy, and S. Cohen Effects of N-propargyl-1-(R)aminoindan (rasagiline) in models of motor and cognition disorders J. Neural Transm. Suppl. 52 1998 287 300
44. J. Sterling, Y. Herzig, T. Goren, N. Finkelstein, D. Lemer, W. Goldenberg, I. Miskolczi, S. Molnar, F. Rantal, T. Tamas, G. Toth, A. Zagyva, A. Zekany, J. Finberg, G. Lavian, A. Gross, R. Friedman, M. Razin, W. Huang, B. Krais, M. Chorev, M.B. Youdim, and M. Weinstock Novel dual inhibitors of AChE and MAO derived from hydroxyl aminoindan and phenethylamine as potential treatment for Alzheimer's disease J. Med. Chem. 45 2002 5260 5267
45. E. Tandberg, J.P. Larsen, D. Aarsland, and J.L. Cummings The occurrence of depression in Parkinson's disease. A community-based study Arch. Neurol. 53 1996 175 179
46. W.G. Tatton, R.M. Chalmers-Redman, W.J. Ju, M. Mammen, G.W. Carlile, A.W. Pong, and N.A. Tatton Propargylamines induce anti-apoptotic new protein synthesis in serum- and nerve growth factor (NGF)-withdrawn, NGF-differentiated PC-12 cells J. Pharmacol. Exp. Ther. 301 2002 753 764
47. W. Tatton, R. Chalmers-Redman, and N. Tatton Neuroprotection by deprenyl and other propargylamines: glyceraldehyde-3-phosphate dehydrogenase rather than monoamine oxidase B J. Neural Transm. 110 2003 509 515
48. O. Weinreb, O. Bar-Am, T. Amit, O. Chillag-Talmor, and M.B. Youdim Neuroprotection via pro-survival protein kinase C isoforms associated with Bcl-2 family members FASEB J. 18 2004 1471 1473
49. M. Weinstock, C. Bejar, R.H. Wang, T. Poltyrev, A. Gross, J.P.M. Finberg, and M.B.H. Youdim TV3326, a novel neuroprotective drug with cholinesterase and monoamine oxidase inhibitory activities for the treatment of Alzheimer's disease J. Neural Transm. 60 Suppl. 2000 157 169
50. M. Weinstock, T. Goren, and M.B.H. Youdim Development of a novel neuroprotective drug (TV3326) for the treatment of Alzheimer's disease, with cholinesterase and monoamine oxidase inhibitory activities Drug Dev. Res. 50 2000 216 222
51. M. Weinstock, N. Kirschbaum-Slager, P. Lazarovici, C. Bejar, M.B.H. Youdim, and S. Shoham Neuroprotective effects of novel cholinesterase inhibitors derived from rasagiline as potential anti-Alzheimer drugs Ann. N. Y. Acad. Sci. 939 2001 148 162
52. M. Weinstock, T. Poltyrev, C. Bejar, and M.B.H. Youdim Effect of TV3326, a novel monoamine-oxidase-cholinesterase inhibitor, in rat models of anxiety and depression Psychopharmacology 160 2002 318 324
53. M. Weinstock, E. Gorodetsky, R.H. Wang, A. Fross, O. Weinreb, and M.B.H. Youdim Limited potentiation of blood pressure response to oral tyramine by brain-selective monoamine oxidase A-B inhibitor, TV-3326 in conscious rabbits Neuropharmacology 43 2002 999-1005
54. M. Weinstock, E. Gorodetsky, T. Poltyrev, A. Gross, Y. Sagi, and M.B.H. Youdim A novel cholinesterase and brain-selective monoamine oxidase inhibitor for the treatment of dementia comorbid with depression and Parkinson's disease Prog. Neuropsychopharmacol. Biol. Psychiatry 27 2003 555 561
55. M. Weinstock, T. Poltyrev, C. Bejar, Y. Sagi, and M.B.H. Youdim TV3326, a novel cholinesterase and MAO inhibitor for Alzheimer's disease with co-morbidity of Parkinson's disease and depression Y. Mizuno A. Fisher I. Hanin Mapping the Progress of Alzheimer's and Parkinson's Disease 2003 Kluwer Academic/Plenum Publishers New York 199-204
56. M. Yogev-Falach, T. Amit, O. Bar-Am, M. Weinstock, and M.B.H. Youdim The involvement of mitogen-activated protein (MAP) kinase in the regulation of amyloid precursor protein processing by novel cholinesterase inhibitors derived from rasagiline FASEB J. 16 2002 1674 1676
57. M. Yogev-Falach, T. Amit, O. Bar-Am, and M.B.H. Youdim The importance of propargylamine moiety in the anti-Parkinson drug rasagiline and its derivatives in MAPK-dependent amyloid precursor protein processing FASEB J. 17 2003 2325 2327
58. M.B.H. Youdim, and M. Weinstock Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug, TV3326 [(n-propargyl-(3r)aminoindan-5-yl)-ethyl methyl carbamate] Cell Mol. Biol. 21 2001 555 573
59. M.B. Youdim, E. Grunblatt, and S. Mandel The pivotal role of iron in NF-kappa B activation and nigrostriatal dopaminergic neurodegeneration. Prospects for neuroprotection in Parkinson's disease with iron chelators Ann. N. Y. Acad. Sci. 890 1999 7 25
60. M.B.H. Youdim, A. Gross, and J.P.M. Finberg Rasagiline [N-Propargyl-1R(+)-aminoindant], a selective and potent inhibitor of mitochondrial monoamine oxidase B Br. J. Pharmacol. 132 2001 500 506
61. M.B.H. Youdim, A. Wadia, N.A. Tatton, and M. Weinstock The antiparkinson drug rasagiline and its derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo Ann. N. Y. Acad. Sci. 939 2001 450 458
62. M.B.H. Youdim Rasagiline; an anti-Parkinson drug with neuroprotective activity Expert Rev. Neurother. 3 2003 737 749
63. M.B.H. Youdim, G. Eshek, and D. Ben Shachar Iron out iron in Parkinson's disease and other neurodegenerative diseases with iron chelators; a lesson from 6-hydroxydoapmine and iron chelaros desferal and VK-28 Ann. N. Y. Acad. Sci. 112 2004 306 325
64. Youdim, M.B.H., Fridkin, M., Zheng, H., in press-c. Novel bifucntional drugs targeting monoamine oxidase and iron chelation as a an approach to neuroprotection in Parkinson's disease and other neurodegeneration diseases. J. Neural. Transm. 111, 1455-1471.
65. Zheng, H., Weiner, L.M., Bar-Am, O., Cabantchik, I., Warshawsky, A., Fridkin, M., Youdim, M.B.H., in press. Design, synthesis and evaluation of novel iron-chelators as potential agents for treatment of neurodegenerative diseases with iron misregulation. Bio. Org. Chem. (in press).