Oral N-Acetyl-cysteine attenuates loss of dopaminergic terminals in α-synuclein overexpressing mice

PLoS ONE

Volumn 5, Issue 8, 2010, Pages

  Clark, Joanne ^a,b   Clore, Elizabeth L ^a   Zheng, Kangni ^a   Adame, Anthony ^c   Masliah, Eliezer ^c   Simon, David K ^a,b  

^a BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCYSTEINE; ALANINE; ALPHA SYNUCLEIN; DOPAMINE TRANSPORTER; GLUTATHIONE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PLATELET DERIVED GROWTH FACTOR B; TYROSINE 3 MONOOXYGENASE; DOPAMINE; NEUROPROTECTIVE AGENT;

AMINO ACID BRAIN LEVEL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CORPUS STRIATUM; DIET SUPPLEMENTATION; DOPAMINERGIC NERVE CELL; FLUID INTAKE; IMMUNOREACTIVITY; MALE; MOUSE; NEUROPROTECTION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; STUDENT T TEST; SUBSTANTIA NIGRA; TRANSGENIC MOUSE; TREATMENT DURATION; TWO TAILED TEST; ANIMAL; CYTOSOL; DRUG EFFECT; GENE EXPRESSION; GENETICS; HUMAN; METABOLISM; MOTOR ACTIVITY; NEOSTRIATUM; ORAL DRUG ADMINISTRATION; PARKINSON DISEASE; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PROTEIN TRANSPORT; TIME;

MUS; MUS MUSCULUS;

ACETYLCYSTEINE; ADMINISTRATION, ORAL; ALPHA-SYNUCLEIN; ANIMALS; CYTOSOL; DIETARY SUPPLEMENTS; DOPAMINE; GENE EXPRESSION; GLUTATHIONE; HUMANS; MALE; MICE; MICE, TRANSGENIC; MOTOR ACTIVITY; NEOSTRIATUM; NEUROPROTECTIVE AGENTS; NF-KAPPA B; PARKINSON DISEASE; PROTEIN TRANSPORT; PROTO-ONCOGENE PROTEINS C-SIS; TIME FACTORS; TYROSINE 3-MONOOXYGENASE;

EID: 77957860419     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0012333     Document Type: Article

References (69)

1. Thomas B, Beal MF (2007) Parkinson's disease. Hum Mol Genet 16(R2): R183-194.
2. Schapira AH (2008) Progress in Parkinson's disease. Eur J Neurol 15(1): 1.
3. Schapira AH, et al. (1992) Mitochondrial function in Parkinson's disease. The Royal Kings and Queens Parkinson's Disease Research Group. Ann Neurol 32(Suppl): S116-24.
4. Greenamyre JT, Betarbet R, Sherer TB (2003) The rotenone model of Parkinson's disease: genes, environment and mitochondria. Parkinsonism Relat Disord 9 Suppl 2: S59-64.
5. Langston JW (1996) The etiology of Parkinson's disease with emphasis on the MPTP story. Neurology 47(6 Suppl 3): S153-60.
6. Cassarino DS, et al. (1997) Elevated reactive oxygen species and antioxidant enzyme activities in animal and cellular models of Parkinson's disease. Biochim Biophys Acta 1362(1): 77-86.
7. Kushnareva Y, Murphy AN, Andreyev A (2002) Complex I-mediated reactive oxygen species generation: modulation by cytochrome c and NAD(P)+ oxidation-reduction state. Biochem J 368(Pt 2): 545-53.
8. Sherer TB, et al. (2002) An In Vitro Model of Parkinson's Disease: Linking Mitochondrial Impairment to Altered α-Synuclein Metabolism and Oxidative Damage. J Neurosci 22(16): 7006-7015.
9. Jenner P (2003) Oxidative stress in Parkinson's disease. Ann Neurol 53 Suppl 3: S26-36; discussion S36-8.
10. Perry TL, Godin DV, Hansen S (1982) Parkinson's disease: a disorder due to nigral glutathione deficiency? Neurosci Lett 33(3): 305-10.
11. Dexter DT, et al. (1994) Increased levels of lipid hydroperoxides in the parkinsonian substantia nigra: an HPLC and ESR study. Mov Disord 9(1): 92-7.
12. Rochet JC, et al. (2004) Interactions among alpha-Synuclein, dopamine, and biomembranes: some clues for understanding neurodegeneration in Parkinson's disease. J Mol Neurosci 23(1-2): 23-34.
13. Xu J, et al. (2002) Dopamine-dependent neurotoxicity of alpha-Synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat Med 8(6): 600-6.
14. Duda JE, et al. (2000) Widespread nitration of pathological inclusions in neurodegenerative synucleinopathies. Am J Pathol 157(5): 1439-45.
15. Souza JM, et al. (2000) Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies. J Biol Chem 275(24): 18344-9.
16. Giasson BI, et al. (2000) Oxidative damage linked to neurodegeneration by selective alpha- synuclein nitration in synucleinopathy lesions. Science 290(5493): 985-9.
17. Hashimoto M, et al. (1999) Oxidative stress induces amyloid-like aggregate formation of NACP/alpha-Synucleinin vitro. Neuroreport 10(4): 717-21.
18. Paxinou E, et al. (2001) Induction of alpha-Synucleinaggregation by intracellular nitrative insult. J Neurosci 21(20): 8053-61.
19. Conway KA, et al. (2001) Kinetic Stabilization of the alpha -Synuclein Protofibril by a Dopamine- alpha -Synuclein Adduct. Science 294(5545): 1346-9.
20. Masliah E, et al. (2000) Dopaminergic loss and inclusion body formation in alpha-Synucleinmice: implications for neurodegenerative disorders. Science 287(5456): 1265-9.
21. Ibanez P, et al. (2004) Causal relation between alpha-Synucleingene duplication and familial Parkinson's disease. Lancet 364(9440): 1169-71.
22. Chartier-Harlin MC, et al. (2004) Alpha-Synucleinlocus duplication as a cause of familial Parkinson's disease. Lancet 364(9440): 1167-9.
23. Singleton AB, et al. (2003) alpha-Synucleinlocus triplication causes Parkinson's disease. Science 302: 841.
24. Dringen R, Hamprecht B (1999) N-acetylcysteine, but not methionine or 2-oxothiazolidine-4-carboxylate, serves as cysteine donor for the synthesis of glutathione in cultured neurons derived from embryonal rat brain. Neurosci Lett 259(2): 79-82.
25. Zafarullah M, et al. (2003) Molecular mechanisms of N-acetylcysteine actions. Cellular and Molecular Life Sciences (CMLS) V60(1): 6-20.
26. Reliene R, Fischer E, Schiestl RH (2004) Effect of N-acetyl cysteine on oxidative DNA damage and the frequency of DNA deletions in atm-deficient mice. Cancer Res 64(15): 5148-53.
27. Pocernich CB, La Fontaine M, Butterfield DA (2000) In-vivo glutathione elevation protects against hydroxyl free radical- induced protein oxidation in rat brain. Neurochem Int 36(3): 185-91.
28. Banaclocha MM (2000) N-acetylcysteine elicited increase in complex I activity in synaptic mitochondria from aged mice: implications for treatment of Parkinson's disease. Brain Res 859(1).
29. Banaclocha MM, et al. (1997) N-acetylcysteine protects against age-related increase in oxidized proteins in mouse synaptic mitochondria. Brain Res 762(1-2): 256-8.
30. Vina J, et al. (1983) Effects of cysteine and N-acetyl cysteine on GSH content of brain of adult rats. Experientia 39(2): 164-5.
31. Sheffner AL, et al. (1966) Metabolic studies with acetylcysteine. Biochem Pharmacol 15(10): 1523-35.
32. Perry TL, et al. (1985) Partial protection from the dopaminergic neurotoxin Nmethyl- 4-phenyl- 1,2,3,6-tetrahydropyridine by four different antioxidants in the mouse. Neurosci Lett 60(2): 109-14.
33. Sharma A, et al. (2007) Attenuation of 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine induced nigrostriatal toxicity in mice by N-acetyl cysteine. Cell Mol Biol (Noisy-le-grand) 53(1): 48-55.
34. Adair JC, Knoefel JE, Morgan N (2001) Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease. Neurology 57(8): 1515-7.
35. Banaclocha MM (2001) Therapeutic potential of N-acetylcysteine in age-related mitochondrial neurodegenerative diseases. Med Hypotheses 56(4): 472-7.
36. Martinez M, et al. (1999) Hypothesis: can N-acetylcysteine be beneficial in Parkinson's disease? Life Sci 64(15): 1253-7.
37. Ravina BM, et al. (2003) Neuroprotective agents for clinical trials in Parkinson's disease: a systematic assessment. Neurology 60(8): 1234-40.
38. Aoyama K, et al. (2006) Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. Nat Neurosci 9(1): 119-26.
39. Liu L, et al. (2010) Ghrelin prevents 1-methyl-4-phenylpyridinium ion-induced cytotoxicity through antioxidation and NF-kappaB modulation in MES23.5 cells. Exp Neurol 222(1): 25-9.
40. Sha D, Chin LS, Li L (2010) Phosphorylation of parkin by Parkinson diseaselinked kinase PINK1 activates parkin E3 ligase function and NF-kappaB signaling. Hum Mol Genet 19(2): 352-63.
41. Aoki E, et al. (2009) Role of nuclear transcription factor kappa B (NF-kappaB) for MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine)-induced apoptosis in nigral neurons of mice. Exp Mol Pathol 86(1): 57-64.
42. Camandola S, Mattson MP (2007) NF-kB as a therapeutic target in neurodegenerative diseases. Expert Opinion on Therapeutic Targets 11(2): 123-132.
43. Khachigian LM, et al. (1995) Nuclear factor-kappa B interacts functionally with the platelet-derived growth factor B-chain shear-stress response element in vascular endothelial cells exposed to fluid shear stress. J Clin Invest 96(2): 1169-75.
44. Shi J, et al. (2004) Roles of NF-kappaB and SP-1 in oxidative stress-mediated induction of platelet-derived growth factor-B by TNFalpha in human endothelial cells. J Cardiovasc Pharmacol 44(1): 26-34.
45. Chesselet MF, et al. (2008) Strengths and limitations of genetic mouse models of Parkinson's disease. Parkinsonism Relat Disord 14(Suppl 2): S84-7.
46. Hashimoto M, Rockenstein E, Masliah E (2003) Transgenic models of alphasynuclein pathology: past, present, and future. Ann N Y Acad Sci 991: 171-88.
47. Hardy J, et al. (2006) Genetics of Parkinson's disease and parkinsonism. Annals of Neurology 60(4): 389-398.
48. Gwinn-Hardy K (2002) Genetics of parkinsonism. Mov Disord 17(4): 645-656.
49. Adams JD Jr, Chang ML, Klaidman L (2001) Parkinson's disease-redox mechanisms. Curr Med Chem 8(7): 809-14.
50. Quilty MC, et al. (2006) Alpha-Synucleinis upregulated in neurones in response to chronic oxidative stress and is associated with neuroprotection. Exp Neurol 199(2): 249-56.
51. Ghosh A, et al. (2007) Selective inhibition of NF-kappaB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A 104(47): 18754-9.
52. Lee H-J, et al. (2010) Direct Transfer of α-Synuclein from Neuron to Astroglia Causes Inflammatory Responses in Synucleinopathies. Journal of Biological Chemistry 285(12): 9262-9272.
53. Gu X-L, et al. (2010) Astrocytic expression of Parkinson's disease-related A53T alpha-Synucleincauses neurodegeneration in mice. Molecular Brain 3(1): 12.
54. Kirik D, et al. (2002) Parkinson-like neurodegeneration induced by targeted overexpression of alpha-Synucleinin the nigrostriatal system. J Neurosci 22(7): 2780-91.
55. Kirik D, et al. (2003) Nigrostriatal alpha-Synucleinopathy induced by viral vector-mediated overexpression of human alpha-Synuclein: a new primate model of Parkinson's disease. Proc Natl Acad Sci U S A 100(5): 2884-9.
56. Richfield EK, et al. (2002) Behavioral and neurochemical effects of wild-type and mutated human alpha-Synucleinin transgenic mice. Exp Neurol 175(1): 35-48.
57. Thiruchelvam MJ, et al. (2004) Risk factors for dopaminergic neuron loss in human alpha-Synucleintransgenic mice. Eur J Neurosci 19(4): 845-54.
58. Zed PJ, Krenzelok EP (1999) Treatment of acetaminophen overdose. Am J Health Syst Pharm 56(11): 1081-91; quiz 1091-3.
59. Andreassen OA, et al. (2000) N-acetyl-L-cysteine improves survival and preserves motor performance in an animal model of familial amyotrophic lateral sclerosis. Neuroreport 11(11): 2491-3.
60. Balansky R, et al. (1996) Induction by carcinogens and chemoprevention by Nacetylcysteine of adducts to mitochondrial DNA in rat organs. Cancer Res 56(7): 1642-7.
61. Tietze F (1969) Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 27(3): 502-22.
62. Griffith OW (1980) Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106(1): 207-12.
63. Vornov JJ, Park J, Thomas AG (1998) Regional vulnerability to endogenous and exogenous oxidative stress in organotypic hippocampal culture. Exp Neurol 149(1): 109-22.
64. Jones BJ, Roberts DJ (1968) The quantitative measurement of motor incoordination in naive mice using an accelerating rotarod. J Pharm Pharmacol 20(4): 302-304.
65. Tillerson JL, et al. (2002) Detection of behavioral impairments correlated to neurochemical deficits in mice treated with moderate doses of 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine. Exp Neurol 178(1): 80-90.
66. Ogawa N, et al. (1985) A simple quantitative bradykinesia test in MPTP-treated mice. Res Commun Chem Pathol Pharmacol 50(3): 435-441.
67. Matsuura K, et al. (1997) Pole test is a useful method for evaluating the mouse movement disorder caused by striatal dopamine depletion. Journal of Neuroscience Methods 73(1): 45-48.
68. Fleming SM, et al. (2004) Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-Synuclein. J Neurosci 24(42): 9434-40.
69. Rommelfanger KS, et al. (2007) Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice. Proceedings of the National Academy of Sciences 104(34): 13804-13809.