Simvastatin inhibits the activation of p21ras and prevents the loss of dopaminergic neurons in a mouse model of Parkinson's disease

Journal of Neuroscience

Volumn 29, Issue 43, 2009, Pages 13543-13556

  Ghosh, Anamitra ^a   Roy, Avik ^a   Matras, Joanna ^a   Brahmachari, Saurav ^a   Gendelman, Howard E ^b   Pahan, Kalipada ^a  

^a RUSH UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MUTANT PROTEIN; NEUROTRANSMITTER; PROTEIN P21; SIMVASTATIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL STIMULATION; CONTROLLED STUDY; DOPAMINERGIC NERVE CELL; DRUG INHIBITION; FOOD AND DRUG ADMINISTRATION; MICROGLIA; MOUSE; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; SUBSTANTIA NIGRA;

1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; AGED; ANIMALS; CELL SURVIVAL; DISEASE MODELS, ANIMAL; DOPAMINE; HUMANS; MALE; MICE; MICE, INBRED C57BL; MOTOR ACTIVITY; NEUROGLIA; NEURONS; NEUROPROTECTIVE AGENTS; NEUROTRANSMITTER AGENTS; NF-KAPPA B; PARKINSON DISEASE; PARKINSONIAN DISORDERS; PRAVASTATIN; PROTO-ONCOGENE PROTEINS P21(RAS); SIMVASTATIN; SUBSTANTIA NIGRA;

EID: 70350555275     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.4144-09.2009     Document Type: Article

References (52)

1. Benner EJ, Mosley RL, Destache CJ, Lewis TB, Jackson-Lewis V, Gorantla S, Nemachek C, Green SR, Przedborski S, Gendelman HE (2004) Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A 101:9435-9440. (Pubitemid 38812892)
2. Bessler H, Djaldetti R, Salman H, Bergman M, Djaldetti M (1999) IL-1 beta, IL-2, IL-6 and TNF-alpha production by peripheral blood mononuclear cells from patients with Parkinson's disease. Biomed Pharmacother 53:141-145. (Pubitemid 29507876)
3. Brahmachari S, Fung YK, Pahan K (2006) Induction of glial fibrillary acidic protein expression in astrocytes by nitric oxide. J Neurosci 26:4930-4939. (Pubitemid 44315335)
4. Brochard V, Combadière B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S (2009) Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest 119:182-192.
5. Dasgupta S, Jana M, Liu X, Pahan K (2003) Role of very-late antigen-4 (VLA-4) in myelin basic protein-primed T cell contact-induced expression of proinflammatory cytokines in microglial cells. J Biol Chem 278:22424-22431. (Pubitemid 36830294)
6. Date I, Yoshimoto Y, Imaoka T, Miyoshi Y, Gohda Y, Furuta T, Asari S, Ohmoto T (1993) Enhanced recovery of the nigrostriatal dopaminergic system in MPTP-treated mice following intrastriatal injection of basic fibroblast growth factor in relation to aging. Brain Res 621:150-154. (Pubitemid 23242175)
7. Dauer W, Przedborski S (2003) Parkinson's disease: mechanisms and models. Neuron 39:889-909.
8. Dehmer T, Lindenau J, Haid S, Dichgans J, Schulz JB (2000) Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J Neurochem 74:2213-2216. (Pubitemid 30217680)
9. Delanty N, Vaughan CJ, Sheehy N (2001) Statins and neuroprotection. Expert Opin Investig Drugs 10:1847-1853.
10. Eng LF, Ghirnikar RS (1994) GFAP and astrogliosis. Brain Pathol 4:229-237.
11. Flanders KC, Ren RF, Lippa CF (1998) Transforming growth factor-betas in neurodegenerative disease. Prog Neurobiol 54:71-85. (Pubitemid 28049820)
12. Gao HM, Liu B, Zhang W, Hong JS (2003) Novel anti-inflammatory therapy for Parkinson's disease. Trends Pharmacol Sci 24:395-401. (Pubitemid 36952555)
13. Garnovskaya MN, van Biesen T, Hawe B, Casañas Ramos S, Lefkowitz RJ, Raymond JR (1996) Ras-dependent activation of fibroblast mitogenactivated protein kinase by 5-HT1A receptor via a G protein beta gamma-subunit-initiated pathway. Biochemistry 35:13716-13722.
14. Ghosh A, Roy A, Liu X, Kordower JH, Mufson EJ, Hartley DM, Ghosh S, Mosley RL, Gendelman HE, Pahan K (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 104:18754-18759. (Pubitemid 350210769)
15. González-Scarano F, Baltuch G (1999) Microglia as mediators of inflammatory and degenerative diseases. Annu Rev Neurosci 22:219-240. (Pubitemid 29144887)
16. Hancock JF, Cadwallader K, Marshall CJ (1991) Methylation and proteolysis are essential for efficient membrane binding of prenylated p21K-ras(B). EMBO J 10:641-646. (Pubitemid 21905518)
17. Hayden MS, Ghosh S (2008) Shared principles in NF-kappaB signaling. Cell 132:344-362.
18. Heumann R, Goemans C, Bartsch D, Lingenhöhl K, Waldmeier PC, Hengerer B, Allegrini PR, Schellander K, Wagner EF, Arendt T, Kamdem RH, Obst-Pernberg K, Narz F, Wahle P, Berns H (2000) Transgenic activation of Ras in neurons promotes hypertrophy and protects from lesion-induced degeneration. J Cell Biol 151:1537-1548. (Pubitemid 32047601)
19. Hunot S, Boissière F, Faucheux B, Brugg B, Mouatt-Prigent A, Agid Y, Hirsch EC (1996) Nitric oxide synthase and neuronal vulnerability in Parkinson's disease. Neuroscience 72:355-363. (Pubitemid 26111202)
20. Hunot S, Brugg B, Ricard D, Michel PP, Muriel MP, Ruberg M, Faucheux BA, Agid Y, Hirsch EC (1997) Nuclear translocation of NF-kappaB is increased in dopaminergic neurons of patients with Parkinson disease. Proc Natl Acad Sci U S A 94:7531-7536. (Pubitemid 27345350)
21. Jana M, Liu X, Koka S, Ghosh S, Petro TM, Pahan K (2001) Ligation of CD40 stimulates the induction of nitric-oxide synthase in microglial cells. J Biol Chem 276:44527-44533. (Pubitemid 37391227)
22. Jana M, Jana A, Liu X, Ghosh S, Pahan K (2007) Involvement of phosphatidylinositol 3-kinase-mediated up-regulation of IκB alpha in anti-inflammatory effect of gemfibrozil in microglia. J Immunol 179:4142-4152.
23. Kordower JH, Palfi S, Chen EY, Ma SY, Sendera T, Cochran EJ, Cochran EJ, Mufson EJ, Penn R, Goetz CG, Comella CD (1999) Clinicopathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson's disease. Ann Neurol 46:419-424. (Pubitemid 29416283)
24. Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor MD, Carvey P, Ling Z, Trono D, Hantraye P, Déglon N, Aebischer P (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science 290:767-773. (Pubitemid 30812168)
25. Kreisler A, Gelé P, Wiart JF, Lhermitte M, Destée A, Bordet R (2007) Lipid-lowering drugs in the MPTP mouse model of Parkinson's disease: fenofibrate has a neuroprotective effect, whereas bezafibrate and HMG-CoA reductase inhibitors do not. Brain Res 1135:77-84. (Pubitemid 46176827)
26. Leftheris K, Kline T, Vite GD, Cho YH, Bhide RS, Patel DV, Patel MM, Schmidt RJ, Weller HN, Andahazy ML, Carboni JM, Gullo-Brown JL, Lee FY, Ricca C, Rose WC, Yan N, Barbacid M, Hunt JT, Meyers CA, Seizinger BR, et al. (1996) Development of highly potent inhibitors of Ras farnesyltransferase possessing cellular and in vivo activity. J Med Chem 39:224-236. (Pubitemid 26027030)
27. Liberatore GT, Jackson-Lewis V, Vukosavic S, Mandir AS, Vila M, McAuliffe WG, Dawson VL, Dawson TM, Przedborski S (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med 5:1403-1409.
28. Liu X, Jana M, Dasgupta S, Koka S, He J, Wood C, Pahan K (2002) Human immunodeficiency virus type 1 (HIV-1) tat induces nitric-oxide synthase in human astroglia. J Biol Chem 277:39312-39319. (Pubitemid 35190903)
29. Markey SP, Johannessen JN, Chiueh CC, Burns RS, Herkenham MA (1984) Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 311:464-467.
30. Mogi M, Harada M, Kondo T, Riederer P, Inagaki H, Minami M, Nagatsu T (1994) Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett 180:147-150. (Pubitemid 2157863)
31. Nagatsu T, Mogi M, Ichinose H, Togari A (2000) Changes in cytokines and neurotrophins in Parkinson's disease. J Neural Transm Suppl 277-290. (Pubitemid 32037200)
32. Olanow CW, Tatton WG (1999) Etiology and pathogenesis of Parkinson's disease. Annu Rev Neurosci 22:123-144.
33. Pahan K (2006) Lipid-lowering drugs. Cell Mol Life Sci 63:1165-1178.
34. Pahan K, Sheikh FG, Namboodiri AM, Singh I (1997) Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. J Clin Invest 100:2671-2679. (Pubitemid 28007534)
35. ras inhibits induction of nitric oxide synthase and activation of nuclear factor-kappaB in primary astrocytes. J Neurochem 74:2288-2295.
36. Qiu RG, Chen J, Kirn D, McCormick F, Symons M (1995) An essential role for Rac in Ras transformation. Nature 374:457-459.
37. Quion JA, Jones PH (1994) Clinical pharmacokinetics of pravastatin. Clin Pharmacokinet 27:94-103.
38. Qureshi GA, Baig S, Bednar I, Södersten P, Forsberg G, Siden A (1995) Increased cerebrospinal fluid concentration of nitrite in Parkinson's disease. Neuroreport 6:1642-1644.
39. Roy A, Fung YK, Liu X, Pahan K (2006) Up-regulation of microglial CD11b expression by nitric oxide. J Biol Chem 281:14971-14980. (Pubitemid 43855201)
40. Saheki A, Terasaki T, Tamai I, Tsuji A (1994) In vivo and in vitro bloodbrain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharm Res 11:305-311.
41. Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK (2009) A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137:47-59.
42. Selley ML (2005) Simvastatin prevents 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-induced striatal dopamine depletion and protein tyrosine nitration in mice. Brain Res 1037:1-6.
43. Sriram K, Matheson JM, Benkovic SA, Miller DB, Luster MI, O'Callaghan JP (2006) Deficiency of TNF receptors suppresses microglial activation and alters the susceptibility of brain regions to MPTP-induced neurotoxicity: role of TNF-alpha. FASEB J 20:670-682. (Pubitemid 44933311)
44. Teismann P, Tieu K, Cohen O, Choi DK, Wu DC, Marks D, Vila M, Jackson-Lewis V, Przedborski S (2003) Pathogenic role of glial cells in Parkinson's disease. Mov Disord 18:121-129. (Pubitemid 36305454)
45. Tieu K, Perier C, Caspersen C, Teismann P, Wu DC, Yan SD, Naini A, Vila M, Jackson-Lewis V, Ramasamy R, Przedborski S (2003) D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J Clin Invest 112:892-901. (Pubitemid 38063747)
46. Tillerson JL, Caudle WM, Reverón ME, Miller GW (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 178:80-90.
47. Vila M, Przedborski S (2004) Genetic clues to the pathogenesis of Parkinson's disease. Nat Med 10 [Suppl]:S58-S62.
48. Vuletic S, Riekse RG, Marcovina SM, Peskind ER, Hazzard WR, Albers JJ (2006) Statins of different brain penetrability differentially affect CSF PLTP activity. Dement Geriatr Cogn Disord 22:392-398. (Pubitemid 44726008)
49. Wahner AD, Bronstein JM, Bordelon YM, Ritz B (2008) Statin use and the risk of Parkinson disease. Neurology 70:1418-1422.
50. Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE (2007) Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Med 5:20. (Pubitemid 47337253)
51. Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, Choi DK, Ischiropoulos H, Przedborski S (2002) Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci 22:1763-1771.
52. Zhao C, Ling Z, Newman MB, Bhatia A, Carvey PM (2007) TNF-alpha knockout and minocycline treatment attenuates blood-brain barrier leakage in MPTP-treated mice. Neurobiol Dis 26:36-46. (Pubitemid 46437443)