Additive Neuroprotective Effects of the Multifunctional Iron Chelator M30 with Enriched Diet in a Mouse Model of Amyotrophic Lateral Sclerosis

Neurotoxicity Research

Volumn 29, Issue 2, 2016, Pages 208-217

  Golko Perez, Sagit ^a   Mandel, Silvia ^a   Amit, Tamar ^a   Kupershmidt, Lana ^a   Youdim, Moussa B H ^a   Weinreb, Orly ^a  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

Author keywords

Amyotrophic lateral sclerosis; Calorie energy supplemented diet; Gastrocnemius muscle; MAO inhibitor iron chelator; Mitochondrial biogenesis metabolism; SOD1 G93A mice

Indexed keywords

5 (N METHYL N PROPARGYLAMINOMETHYL) 8 HYDROXYQUINOLINE; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME A; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME B; DOPAMINE; INSULIN RECEPTOR; IRON CHELATING AGENT; MESSENGER RNA; NEUROPROTECTIVE AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN 1; 3,4 DIHYDROXYPHENYLACETIC ACID; 5-(N-METHYL-N-PROPARGYLAMINOMETHYL)-8-HYDROXYQUINOLINE; AMINE OXIDASE (FLAVIN CONTAINING); BIOGENIC AMINE; COPPER ZINC SUPEROXIDE DISMUTASE; MONOAMINE OXIDASE INHIBITOR; PHENYLACETIC ACID DERIVATIVE; PPARGC1A PROTEIN, MOUSE; QUINOLINOL DERIVATIVE; SOD1 PROTEIN, MOUSE; SUPEROXIDE DISMUTASE; TRANSCRIPTION FACTOR;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOGENESIS; CONTROLLED STUDY; DIET SUPPLEMENTATION; DOPAMINE METABOLISM; ENERGY METABOLISM; ENZYME INHIBITION; GASTROCNEMIUS MUSCLE; GENE EXPRESSION REGULATION; INSULIN RECEPTOR GENE; LIFE EXTENSION; MALE; MITOCHONDRIAL RESPIRATION; MOTOR PERFORMANCE; MOUSE; NEUROPROTECTION; NONHUMAN; PGC 1ALPHA GENE; PPAR GAMMA GENE; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; UNCOUPLING PROTEIN 1 GENE; UPREGULATION; ANIMAL; CORPUS STRIATUM; DIET; DISEASE MODEL; DRUG EFFECTS; GENETICS; METABOLISM; MOTOR ACTIVITY; PATHOPHYSIOLOGY; SURVIVAL ANALYSIS; TRANSGENIC MOUSE;

3,4-DIHYDROXYPHENYLACETIC ACID; AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; BIOGENIC MONOAMINES; CORPUS STRIATUM; DIET; DISEASE MODELS, ANIMAL; HYDROXYQUINOLINES; IRON CHELATING AGENTS; MALE; MICE; MICE, TRANSGENIC; MONOAMINE OXIDASE; MONOAMINE OXIDASE INHIBITORS; MOTOR ACTIVITY; NEUROPROTECTIVE AGENTS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA COACTIVATOR 1-ALPHA; PHENYLACETATES; SUPEROXIDE DISMUTASE; SUPEROXIDE DISMUTASE-1; SURVIVAL ANALYSIS; TRANSCRIPTION FACTORS;

EID: 84954402997     PISSN: 10298428     EISSN: 14763524     Source Type: Journal    
DOI: 10.1007/s12640-015-9574-4     Document Type: Article

References (63)

1. Adhihetty PJ, Beal MF (2008) Creatine and its potential therapeutic value for targeting cellular energy impairment in neurodegenerative diseases. Neuromolecular Med 10:275–290. doi:10.1007/s12017-008-8053-y
2. Azzouz M, Hottinger A, Paterna JC, Zurn AD, Aebischer P, Bueler H (2000) Increased motoneuron survival and improved neuromuscular function in transgenic ALS mice after intraspinal injection of an adeno-associated virus encoding Bcl-2. Hum Mol Genet 9:803–811
3. Bastos AF, Orsini M, Machado D, Mello MP, Nader S, Silva JG, da Silva Catharino AM, de Freitas MR, Pereira A, Pessoa LL, Sztajnbok FR, Leite MA, Nascimento OJ, Bastos VH (2011) Amyotrophic lateral sclerosis: one or multiple causes? Neurol Int 3:e4. doi:10.4081/ni.2011.e4
4. Benkler C, Offen D, Melamed E, Kupershmidt L, Amit T, Mandel S, Youdim MB, Weinreb O (2010) Recent advances in amyotrophic lateral sclerosis research: perspectives for personalized clinical application. EPMA J 1(2):343–361. doi:10.1007/s13167-010-0026-1
5. Bryson JB, Hobbs C, Parsons MJ, Bosch KD, Pandraud A, Walsh FS, Doherty P, Greensmith L (2012) Amyloid precursor protein (APP) contributes to pathology in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Hum Mol Genet 21:3871–3882. doi:10.1093/hmg/dds215
6. Carri MT, Ferri A, Cozzolino M, Calabrese L, Rotilio G (2003) Neurodegeneration in amyotrophic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals. Brain Res Bull 61:365–374
7. Cleveland DW, Rothstein JD (2001) From charcot to lou gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci 2:806–819
8. Combs DJ, D’Alecy LG (1987) Motor performance in rats exposed to severe forebrain ischemia: effect of fasting and 1,3-butanediol. Stroke 18:503–511
9. Cryan JF, Mombereau C, Vassout A (2005) The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev 29:571–625
10. Dorst J, Cypionka J, Ludolph AC (2013) High-caloric food supplements in the treatment of amyotrophic lateral sclerosis: a prospective interventional study. Amyotroph Lateral Scler Frontotemporal Degener 14:533–536. doi:10.3109/21678421.2013.823999
11. Funalot B, Desport JC, Sturtz F, Camu W, Couratier P (2009) High metabolic level in patients with familial amyotrophic lateral sclerosis. Amyotroph Lateral Scler 10:113–117
12. Gal S, Zheng H, Fridkin M, Youdim MB (2005) 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 95:79–88
13. Garbuzova-Davis S, Willing AE, Milliken M, Saporta S, Sowerby B, Cahill DW, Sanberg PR (2001) Intraspinal implantation of hNT neurons into SOD1 mice with apparent motor deficit. Amyotroph Lateral Scler Other Motor Neuron Disord 2:175–180. doi:10.1080/14660820152882179
14. Genton L, Viatte V, Janssens JP, Heritier AC, Pichard C (2011) Nutritional state, energy intakes and energy expenditure of amyotrophic lateral sclerosis (ALS) patients. Clin Nutr 30:553–559. doi:10.1016/j.clnu.2011.06.004
15. Gurney ME (1997) The use of transgenic mouse models of amyotrophic lateral sclerosis in preclinical drug studies. J Neurol Sci 152(Suppl 1):S67–73
16. Ignjatovic A, Stevic Z, Lavrnic D, Nikolic-Kokic A, Blagojevic D, Spasic M, Spasojevic I (2012) Inappropriately chelated iron in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler 13(4):357–362
17. Ikeda K, Hirayama T, Takazawa T, Kawabe K, Iwasaki Y (2012) Relationships between disease progression and serum levels of lipid, urate, creatinine and ferritin in Japanese patients with amyotrophic lateral sclerosis: a cross-sectional study. Intern Med 51:1501–1508
18. Imon Y, Yamaguchi S, Yamamura Y, Tsuji S, Kajima T, Ito K, Nakamura S (1995) Low intensity areas observed on T2-weighted magnetic resonance imaging of the cerebral cortex in various neurological diseases. J Neurol Sci 134(Suppl):27–32
19. Ince PG, Shaw PJ, Candy JM, Mantle D, Tandon L, Ehmann WD, Markesbery WR (1994) Iron, selenium and glutathione peroxidase activity are elevated in sporadic motor neuron disease. Neurosci Lett 182:87–90
20. Jeong SY, Rathore KI, Schulz K, Ponka P, Arosio P, David S (2009) Dysregulation of iron homeostasis in the CNS contributes to disease progression in a mouse model of amyotrophic lateral sclerosis. J Neurosci 29:610–619
21. Kasarskis EJ, Tandon L, Lovell MA, Ehmann WD (1995) Aluminum, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a preliminary study. J Neurol Sci 130(2):203–208
22. Klivenyi P, Kiaei M, Gardian G, Calingasan NY, Beal MF (2004) Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral s1clerosis. J Neurochem 88:576–582.
23. Klopstock T, Elstner M, Bender A (2011) Creatine in mouse models of neurodegeneration and aging. Amino Acids 40:1297–1303. doi:10.1007/s00726-011-0850-1
24. Kriz J, Gowing G, Julien JP (2003) Efficient three-drug cocktail for disease induced by mutant superoxide dismutase. Ann Neurol 53(4):429–436. doi:10.1002/ana.10500
25. Kumar MJ, Andersen JK (2004) Perspectives on MAO-B in aging and neurological disease: where do we go from here? Mol Neurobiol 30:77–89
26. Kupershmidt L, Weinreb O, Amit T, Mandel S, Carri MT, Youdim MB (2009) 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 23:3766–3779
27. Kupershmidt L, Amit T, Bar-Am O, Youdim MB, Weinreb O (2012a) Neuroprotection by the multitarget iron chelator M30 on age-related alterations in mice. Mech Ageing Dev 133:267–274
28. Kupershmidt L, Amit T, Bar-Am O, Youdim MB, Weinreb O (2012b) 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
29. Kwan JY, Jeong SY, Van Gelderen P, Deng HX, Quezado MM, Danielian LE, Butman JA, Chen L, Bayat E, Russell J, Siddique T, Duyn JH, Rouault TA, Floeter MK (2012) Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathology. PLoS ONE 7:e35241
30. Lawler JM, Barnes WS, Wu G, Song W, Demaree S (2002) Direct antioxidant properties of creatine. Biochem Biophys Res Commun 290:47–52. doi:10.1006/bbrc.2001.6164
31. Liang H, Ward WF, Jang YC, Bhattacharya A, Bokov AF, Li Y, Jernigan A, Richardson A, Van Remmen H (2011) PGC-1alpha protects neurons and alters disease progression in an amyotrophic lateral sclerosis mouse model. Muscle Nerve 44:947–956. doi:10.1002/mus.22217
32. Lowell BB, Spiegelman BM (2000) Towards a molecular understanding of adaptive thermogenesis. Nature 404:652–660. doi:10.1038/35007527
33. Ludolph AC, Bendotti C, Blaugrund E, Hengerer B, Loffler JP, Martin J, Meininger V, Meyer T, Moussaoui S, Robberecht W, Scott S, Silani V, Van Den Berg LH (2007) Guidelines for the preclinical in vivo evaluation of pharmacological active drugs for ALS/MND: report on the 142nd ENMC international workshop. Amyotroph Lateral Scler 8:217–223. doi:10.1080/17482960701292837
34. Mechlovich D, Amit T, Bar-Am O, Weinreb O, Youdim MB (2014) Molecular targets of the multifunctional iron-chelating drug, M30, in the brains of mouse models of type 2 diabetes mellitus. Br J Pharmacol 171:5636–5649. doi:10.1111/bph.12862
35. Musaro A (2013) Understanding ALS: new therapeutic approaches. FEBS J 280:4315–4322. doi:10.1111/febs.12087
36. Muyderman H, Chen T (2014) Mitochondrial dysfunction in amyotrophic lateral sclerosis—a valid pharmacological target? Br J Pharmacol 171:2191–2205. doi:10.1111/bph.12476
37. Oba H, Araki T, Ohtomo K, Monzawa S, Uchiyama G, Koizumi K, Nogata Y, Kachi K, Shiozawa Z, Kobayashi M (1993) Amyotrophic lateral sclerosis: T2 shortening in motor cortex at MR imaging. Radiology 189:843–846
38. Olesen J, Kiilerich K, Pilegaard H (2010) PGC-1alpha-mediated adaptations in skeletal muscle. Pflugers Arch 460:153–162. doi:10.1007/s00424-010-0834-0
39. Palamiuc L, Schlagowski A, Ngo ST, Vernay A, Dirrig-Grosch S, Henriques A, Boutillier AL, Zoll J, Echaniz-Laguna A, Loeffler JP, Rene F (2015) A metabolic switch toward lipid use in glycolytic muscle is an early pathologic event in a mouse model of amyotrophic lateral sclerosis. EMBO Mol Med 7:526–546. doi:10.15252/emmm.201404433
40. Puigserver P, Spiegelman BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24:78–90. doi:10.1210/er.2002-0012
41. Rio A, Cawadias E (2007) Nutritional advice and treatment by dietitians to patients with amyotrophic lateral sclerosis/motor neurone disease: a survey of current practice in England, Wales, Northern Ireland and Canada. J Hum Nutr Diet 20:3–13. doi:10.1111/j.1365-277X.2007.00745.x
42. Rippon GA, Scarmeas N, Gordon PH, Murphy PL, Albert SM, Mitsumoto H, Marder K, Rowland LP, Stern Y (2006) An observational study of cognitive impairment in amyotrophic lateral sclerosis. Arch Neurol 63:345–352
43. Rona-Voros K, Weydt P (2010) The role of PGC-1alpha in the pathogenesis of neurodegenerative disorders. Curr Drug Targets 11:1262–1269
44. Sasaki S, Iwata M (1999) Ultrastructural change of synapses of Betz cells in patients with amyotrophic lateral sclerosis. Neurosci Lett 268:29–32
45. Schmitt F, Hussain G, Dupuis L, Loeffler JP, Henriques A (2014) A plural role for lipids in motor neuron diseases: energy, signaling and structure. Front Cell Neurosci 8:25. doi:10.3389/fncel.2014.00025
46. Scott S, Kranz JE, Cole J, Lincecum JM, Thompson K, Kelly N, Bostrom A, Theodoss J, Al-Nakhala BM, Vieira FG, Ramasubbu J, Heywood JA (2008) Design, power, and interpretation of studies in the standard murine model of ALS. Amyotroph Lateral Scler 9:4–15
47. Siklos L, Engelhardt J, Harati Y, Smith RG, Joo F, Appel SH (1996) Ultrastructural evidence for altered calcium in motor nerve terminals in amyotropic lateral sclerosis. Ann Neurol 39:203–216. doi:10.1002/ana.410390210
48. Song W, Song Y, Kincaid B, Bossy B, Bossy-Wetzel E (2013) Mutant SOD1G93A triggers mitochondrial fragmentation in spinal cord motor neurons: neuroprotection by SIRT3 and PGC-1alpha. Neurobiol Dis 51:72–81. doi:10.1016/j.nbd.2012.07.004
49. St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S, Handschin C, Zheng K, Lin J, Yang W, Simon DK, Bachoo R, Spiegelman BM (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127:397–408. doi:10.1016/j.cell.2006.09.024
50. Tipton KF, McCrodden JM, Kalir AS, Youdim MBH (1982) Inhibition of rat liver monoamine oxidase by alpha-methyl- and N-propargyl-amine derivatives. Biochem Pharmacol 31:1251–1255
51. Tsunemi T, La Spada AR (2012) PGC-1alpha at the intersection of bioenergetics regulation and neuron function: from Huntington’s disease to Parkinson’s disease and beyond. Prog Neurobiol 97:142–151. doi:10.1016/j.pneurobio.2011.10.004
52. Urushitani M, Ezzi SA, Julien JP (2007) Therapeutic effects of immunization with mutant superoxide dismutase in mice models of amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 104:2495–2500
53. Vaisman N, Lusaus M, Nefussy B, Niv E, Comaneshter D, Hallack R, Drory VE (2009) Do patients with amyotrophic lateral sclerosis (ALS) have increased energy needs? J Neurol Sci 279:26–29
54. Veyrat-Durebex C, Corcia P, Mucha A, Benzimra S, Mallet C, Gendrot C, Moreau C, Devos D, Piver E, Pages JC, Maillot F, Andres CR, Vourc’h P, Blasco H (2014) Iron metabolism disturbance in a French cohort of ALS patients. Biomed Res Int 2014:485723–485729. doi:10.1155/2014/485723
55. Vielhaber S, Kunz D, Winkler K, Wiedemann FR, Kirches E, Feistner H, Heinze HJ, Elger CE, Schubert W, Kunz WS (2000) Mitochondrial DNA abnormalities in skeletal muscle of patients with sporadic amyotrophic lateral sclerosis. Brain 123:1339–1348
56. Villena JA (2015) New insights into PGC-1 coactivators: redefining their role in the regulation of mitochondrial function and beyond. FEBS J 282:647–672. doi:10.1111/febs.13175
57. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM (1992) Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J 281:21–40
58. Wang Q, Zhang X, Chen S, Zhang X, Zhang S, Youdium M, Le W (2011) Prevention of motor neuron degeneration by novel iron chelators in SOD1G93A transgenic mice of amyotrophic lateral sclerosis. Neurodegener Dis 8:310–321
59. Wiedemann FR, Manfredi G, Mawrin C, Beal MF, Schon EA (2002) Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients. J Neurochem 80:616–625
60. Winkler EA, Sengillo JD, Sagare AP, Zhao Z, Ma Q, Zuniga E, Wang Y, Zhong Z, Sullivan JS, Griffin JH, Cleveland DW, Zlokovic BV (2014) Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice. Proc Natl Acad Sci USA 111:E1035–1042. doi:10.1073/pnas.1401595111
61. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124. doi:10.1016/S0092-8674(00)80611-X
62. Zhang W, Narayanan M, Friedlander RM (2003) Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann Neurol 53:267–270. doi:10.1002/ana.10476
63. Zhao W, Varghese M, Yemul S, Pan Y, Cheng A, Marano P, Hassan S, Vempati P, Chen F, Qian X, Pasinetti GM (2011) Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1alpha) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis. Mol Neurodegener 6:51–59. doi:10.1186/1750-1326-6-51