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Role of HMG-CoA Reductase Inhibitors in Neurological Disorders

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Abstract

Inhibitors of HMG-CoA reductase (statins) are cholesterol-lowering agents that dramatically reduce morbidity and mortality in patients with established cardiovascular disease. In addition, they exhibit pleiotropic effects that operate independently of lipid modification. Statin administration results in greater nitric oxide bioavailability, improved endothelial function, enhanced cerebral blood flow, immune modulation with anti-inflammatory action, decreased platelet aggregation and antioxidant activity. Some or all of these effects may improve outcome or ameliorate symptoms in neurological disorders. This article examines the potential role of statins in treating stroke, Alzheimer’s disease, multiple sclerosis and Parkinson’s disease. Studies are ongoing in this controversial area, but there are no firm conclusions. The appropriateness of initiating statin therapy for neurological disorders is not established at this time. The exception is stroke, in which recurrence is significantly reduced by statin therapy.

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References

  1. Walker JF. HMG-CoA reductase inhibitors: current clinical experience. Drugs 1988; 36 Suppl. 3: 83–6

    Article  Google Scholar 

  2. Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science 2001 May 11; 292(5519): 1160–4

    Article  PubMed  CAS  Google Scholar 

  3. Hackam DG. Intensive reduction of low-density lipoprotein-cholesterol: implications of recent trials. Am J Cardiovasc Drugs 2006; 6(6): 367–71

    Article  PubMed  CAS  Google Scholar 

  4. Fonarow GC, Watson KE. Effective strategies for long-term statin use. Am J Cardiol 2003 Jul 3; 92(1A): 27–34i

    Article  Google Scholar 

  5. Shepherd J. Who should receive a statin these days? Lessons from recent clinical trials. J Intern Med 2006 Oct; 260(4): 305–19

    Article  PubMed  CAS  Google Scholar 

  6. de Lorenzo F, Feher M, Martin J, et al. Statin therapy-evidence beyond lipid lowering contributing to plaque stability. Curr Med Chem 2006 Dec; 13(28): 3385–93

    Article  PubMed  Google Scholar 

  7. Ray KK, Cannon CP. Early time to benefit with intensive statin treatment: could it be the pleiotropic effects? Am J Cardiol 2005 Sep 5; 96(5A): 54F–60F

    Article  PubMed  CAS  Google Scholar 

  8. Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol 2001 Nov; 21(11): 1712–9

    Article  PubMed  CAS  Google Scholar 

  9. Blanco-Colio LM, Tunon J, Martin-Ventura JL, et al. Anti-inflammatory and immunomodulatory effects of statins. Kidney Int 2003 Jan; 63(1): 12–23

    Article  PubMed  CAS  Google Scholar 

  10. Undas A, Brummel KE, Musial J, et al. Simvastatin depresses blood clotting by inhibiting activation of prothrombin, factor V, and factor XIII and by enhancing factor Va inactivation. Circulation 2001 May 8; 103(18): 2248–53

    Article  PubMed  CAS  Google Scholar 

  11. Essig M, Nguyen G, Prie D, et al. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase fibrinolytic activity in rat aortic endothelial cells: role of geranylgeranylation and Rho proteins. Circ Res 1998 Oct 5; 83(7): 683–90

    Article  PubMed  CAS  Google Scholar 

  12. Shabanzadeh AP, Shuaib A, Wang CX. Simvastatin reduced ischemic brain injury and perfusion deficits in an embolic model of stroke. Brain Res 2005 Apr 25; 1042(1): 1–5

    Article  PubMed  CAS  Google Scholar 

  13. Pozo M, de Nicolas R, Egido J, et al. Simvastatin inhibits the migration and adhesion of monocytic cells and disorganizes the cytoskeleton of activated endothelial cells. Eur J Pharmacol 2006 Oct 24; 548(1-3): 53–63

    Article  PubMed  CAS  Google Scholar 

  14. Gao L, Wang W, Li YL, et al. Simvastatin therapy normalizes sympathetic neural control in experimental heart failure: roles of angiotensin II type 1 receptors and NAD(P)H oxidase. Circulation 2005 Sep 20; 112(12): 1763–70

    Article  PubMed  CAS  Google Scholar 

  15. Chen J, Zhang ZG, Li Y, et al. Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke. Ann Neurol 2003 Jun; 53(6): 743–51

    Article  PubMed  CAS  Google Scholar 

  16. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature 1990 Feb 1; 343(6257): 425–30

    Article  PubMed  CAS  Google Scholar 

  17. Laufs U, Liao JK. Targeting Rho in cardiovascular disease. Circ Res 2000 Sep 29; 87(7): 526–28

    Article  PubMed  CAS  Google Scholar 

  18. Brown JH, Del Re DP, Sussman MA. The Rac and Rho hall of fame: a decade of hypertrophic signaling hits. Circ Res 2006 Mar 31; 98(6): 730–42

    Article  PubMed  CAS  Google Scholar 

  19. Peng X, Jin J, Giri S, et al. Immunomodulatory effects of 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors, potential therapy for relapsing remitting multiple sclerosis. J Neuroimmunol 2006 Sep; 178(1-2): 130–9

    Article  PubMed  CAS  Google Scholar 

  20. Sola S, Mir MQ, Rajagopalan S, et al. Statin therapy is associated with improved cardiovascular outcomes and levels of inflammatory markers in patients with heart failure. J Card Fail 2005 Oct; 11(8): 607–12

    Article  PubMed  CAS  Google Scholar 

  21. Wiklund O, Mattsson-Hulten L, Hurt-Camejo E, et al. Effects of simvastatin and atorvastatin on inflammation markers in plasma. J Intern Med 2002 Apr; 251(4): 338–47

    Article  PubMed  CAS  Google Scholar 

  22. Friedhoff LT, Cullen EI, Geoghagen NS, et al. Treatment with controlled-release lovastatin decreases serum concentrations of human β-amyloid (Aβ) peptide. Int J Neuropsychopharmacol 2001 Jun; 4(2): 127–30

    Article  PubMed  CAS  Google Scholar 

  23. Devaraj S, Rogers J, Jialal I. Statins and biomarkers of inflammation. Curr Atheroscler Rep 2007 Jan; 9(1): 33–41

    Article  PubMed  CAS  Google Scholar 

  24. Stankovic G, Sparks DL. Change in circulating C-reactive protein is not associated with atorvastatin treatment in Alzheimer’s disease. Neurol Res 2006 Sep; 28(6): 621–4

    Article  PubMed  CAS  Google Scholar 

  25. Wolfrum S, Dendorfer A, Schutt M, et al. Simvastatin acutely reduces myocardial reperfusion injury in vivo by activating the phosphatidylinositide 3-kinase/Akt pathway. J Cardiovasc Pharmacol 2004 Sep; 44(3): 348–55

    Article  PubMed  CAS  Google Scholar 

  26. Laufs U, Liao JK. Post-transcriptional regulation of endothelialnitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 1998 Sep 11; 273(37): 24266–71

    Article  PubMed  CAS  Google Scholar 

  27. Harrison DG. Cellular and molecular mechanisms of endothelial cell dysfunction. J Clin Invest 1997 Nov 1; 100(9): 2153–7

    Article  PubMed  CAS  Google Scholar 

  28. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 1989 May; 83(5): 1774–7

    Article  PubMed  CAS  Google Scholar 

  29. Alheid U, Frolich JC, Forstermann U. Endothelium-derived relaxing factor from cultured human endothelial cells inhibits aggregation of human platelets. Thromb Res 1987 Sep 1; 47(5): 561–71

    Article  PubMed  CAS  Google Scholar 

  30. Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 1991 Jun 1; 88(11): 4651–5

    Article  PubMed  CAS  Google Scholar 

  31. Wolfrum S, Jensen K, Liao J. Endothelium-dependent effects of statins. Arterioscler Thromb Vasc Biol 2003 May 1; 23(5): 729–36

    Article  PubMed  CAS  Google Scholar 

  32. Mason JC. Statins and their role in vascular protection. Clin Sci (Lond) 2003 Sep; 105(3): 251–66

    Article  CAS  Google Scholar 

  33. Libby P, Aikawa M. Mechanisms of plaque stabilization with statins. Am J Cardiol 2003 Feb 20; 91(4A): 4–8B

    Article  CAS  Google Scholar 

  34. Vaughan CJ, Gotto Jr AM, Basson CT. The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol 2000 Jan; 35(1): 1–10

    Article  PubMed  CAS  Google Scholar 

  35. Rosenson RS. Pluripotential mechanisms of cardioprotection with HMG-CoA reductase inhibitor therapy. Am J Cardiovasc Drugs 2001; 1(6): 411–20

    Article  PubMed  CAS  Google Scholar 

  36. Rogler G, Lackner KJ, Schmitz G. Effects of fluvastatin on growth of porcine and human vascular smooth muscle cell in vitro. Am J Cardiol. 1995 Jul 13; 76(2): 114–116A

    Article  Google Scholar 

  37. Heart Protection Study Collaborative Group. Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002 Jul 6; 360(9326): 7–22

    Article  Google Scholar 

  38. Corvol JC, Bouzamondo A, Sirol M, et al. Differential effects of lipid-lowering therapies on stroke prevention: a meta-analysis of randomized trials. Arch Intern Med 2003 Mar 24; 163(6): 669–76

    Article  PubMed  CAS  Google Scholar 

  39. Amarenco P, Bogousslavsky J, Callahan 3rd A, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006 Aug 10; 355(6): 549–59

    Article  PubMed  CAS  Google Scholar 

  40. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996 Oct 3; 335(14): 1001–9

    Article  PubMed  CAS  Google Scholar 

  41. Plehn JF, Davis BR, Sacks FM, et al. Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. Circulation 1999 Jan 19; 99(2): 216–23

    Article  PubMed  CAS  Google Scholar 

  42. Stolar M. Metabolic syndrome: controversial but useful. Cleve Clin J Med 2007 Mar; 74(3): 199–202, 205–8

    Article  PubMed  Google Scholar 

  43. Devaraj S, Chan E, Jialal I. Direct demonstration of an antiin-flammatory effect of simvastatin in subjects with the metabolic syndrome. J Clin Endocrinol Metab 2006 Nov; 91(11): 4489–96

    Article  PubMed  CAS  Google Scholar 

  44. Parnetti L, Caso V, Lanari A, et al. Stroke prevention and statin treatment. Clin Exp Hypertens 2006 Apr-May; 28(3-4): 335–44

    Article  PubMed  CAS  Google Scholar 

  45. Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003 Apr 5; 361(9364): 1149–58

    Article  PubMed  CAS  Google Scholar 

  46. Atkins D, Psaty BM, Koepsell D, et al. Cholesterol reduction and the risk for stroke in men: a meta analysis of randomized, controlled trials. Ann Intern Med. 1993 Jul 15; 119(2): 136–45

    PubMed  CAS  Google Scholar 

  47. Alvarez-Sabin J, Huertas R, Quintana M, et al. Prior statin use may be associated with improved stroke outcome after tissue plasminogen activator. Stroke 2007 Mar; 38(3): 1076–8

    Article  PubMed  CAS  Google Scholar 

  48. Engstrom G, Lind P, Hedblad B, et al. Effects of cholesterol and inflammation-sensitive plasma proteins on incidence of myocardial infarction and stroke in men. Circulation 2002 Jun 4; 105(22): 2632–7

    Article  PubMed  CAS  Google Scholar 

  49. Ridker PM, Rifai N, Rose L, et al. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002 Nov 14; 347(20): 1557–65

    Article  PubMed  CAS  Google Scholar 

  50. Vaughan CJ, Delanty N. Neuroprotective properties of statins in cerebral ischemia and stroke. Stroke 1999 Sep; 30(9): 1969–73

    Article  PubMed  CAS  Google Scholar 

  51. Stepien K, Tomaszewski M, Czuczwar SJ. Neuroprotective properties of statins. Pharmacol Rep 2005 Sep-Oct; 57(5): 561–9

    PubMed  CAS  Google Scholar 

  52. Cipollone F, Mezzetti A, Porreca E. Association between enhanced soluble CD40L and prothrombotic state in hyperc-holesterolemia: effects of statin therapy. Circulation 2002 Jul 23; 106(4): 399–402

    Article  PubMed  CAS  Google Scholar 

  53. Chen J, Chopp M. Neurorestorative treatment of stroke: cell and pharmacological approaches. NeuroRx 2006 Oct; 3(4): 466–73

    Article  PubMed  CAS  Google Scholar 

  54. Smaha LA, American Heart Association. The American Heart Association get with the guidelines program. Am Heart J 2004 Nov; 148 (5 Suppl.): S46–48

    Article  PubMed  Google Scholar 

  55. Caselli RJ, Beach TG, Yaari R, et al. Alzheimer’s disease a century later. J Clin Psychiatry 2006 Nov; 67(11): 1784–800

    Article  PubMed  CAS  Google Scholar 

  56. Bianchetti A, Ranieri P, Margiotta A, et al. Pharmacological treatment of Alzheimer’s disease. Aging Clin Exp Res 2006 Apr; 18(2): 158–62

    PubMed  CAS  Google Scholar 

  57. Golde TE. Disease modifying therapy for AD? J Neurochem 2006 Nov; 99(3): 689–707

    Article  PubMed  CAS  Google Scholar 

  58. Hardy J. Alzheimer’s disease: the amyloid cascade hypothesis. An update and reappraisal. J Alzheimers Dis 2006; 9 (3 Suppl.): 151–3

    PubMed  CAS  Google Scholar 

  59. Pastorino L, Lu KP. Pathogenic mechanisms in Alzheimer’s disease. Eur J Pharmacol 2006 Sep 1; 545(1): 29–38

    Article  PubMed  CAS  Google Scholar 

  60. Puglielli L, Tanzi RE, Kovacs DM. Alzheimer’s disease: the cholesterol connection. Nat Neurosci 2003 Apr; 6(4): 345–51

    Article  PubMed  CAS  Google Scholar 

  61. Ehehalt R, Keller P, Haass C, et al. Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts. J Cell Biol 2003 Jan 6; 160(1): 113–23

    Article  PubMed  CAS  Google Scholar 

  62. Panza F, D’Introno A, Colacicco AM, et al. Lipid metabolism in cognitive decline and dementia. Brain Res Brain Res Rev 2006 Aug; 51(2): 275–92

    Article  CAS  Google Scholar 

  63. Notkola IL, Sulkava R, Pekkanen J, et al. Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer’s disease. Neuroepidemiology 1998; 17(1): 14–20

    Article  PubMed  CAS  Google Scholar 

  64. DeKosky ST. Statin therapy in the treatment of Alzheimer disease: what is the rationale? Am J Med 2005 Dec; 118 Suppl. 12A: 48–53

    Article  PubMed  CAS  Google Scholar 

  65. Pappolla MA, Bryant-Thomas TK, Herbert D, et al. Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology. Neurology 2003 Jul 22; 61(2): 199–205

    Article  PubMed  CAS  Google Scholar 

  66. Mielke MM, Zandi PP, Sjogren M, et al. High total cholesterol levels in late life associated with a reduced risk of dementia. Neurology 2005 May 24; 64(10): 1689–95

    Article  PubMed  CAS  Google Scholar 

  67. Li G, Shofer JB, Kukull WA, et al. Serum cholesterol and risk of Alzheimer disease: a community-based cohort study. Neurology 2005 Oct 11; 65(7): 1045–50

    Article  PubMed  CAS  Google Scholar 

  68. Wood WG, Igbavboa U, Eckert GP, et al. Is hypercholesterolemia a risk factor for Alzheimer’s disease? Mol Neurobiol 2005; 31(1-3): 185–92

    Article  PubMed  CAS  Google Scholar 

  69. LaDu MJ, Reardon C, Van Eldik L, et al. Lipoproteins in the central nervous system. Ann NY Acad Sci 2000 Apr; 903: 167–75

    Article  PubMed  CAS  Google Scholar 

  70. Martins CA, Oulhaj A, De Jager CA, et al. APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model. Neurology 2005 Dec 27; 65(12): 1888–93

    Article  PubMed  CAS  Google Scholar 

  71. Sing CF, Davignon J. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet 1985 Mar; 37(2): 268–85

    PubMed  CAS  Google Scholar 

  72. Hoshino T, Kamino K, Matsumoto M. Gene dose affect of the APOE4 allele on plasma HDL cholesterol level in patients with Alzheimer’s disease. Neurobiol Aging 2002 Jan-Feb; 23(1): 41–5

    Article  PubMed  CAS  Google Scholar 

  73. Wolozin B, Kellman W, Ruosseau P, et al. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000 Oct; 57(10): 1439–43

    Article  PubMed  CAS  Google Scholar 

  74. Jick H, Zornberg GL, Jick SS, et al. Statins and the risk of dementia. Lancet 2000 Nov 11; 356(9242): 1627–31

    Article  PubMed  CAS  Google Scholar 

  75. Fassbender K, Simons M, Bergmann C, et al. Simvastatin strongly reduces levels of Alzheimer’s disease ?-amyloid peptides A? 42 and A? 40 in vitro and in vivo. Proc Natl Acad Sci USA 2001 May 8; 98(10): 5856–61

    Article  PubMed  CAS  Google Scholar 

  76. Chauhan NB, Siegel GJ, Feinstein DL. Effects of lovastatin and pravastatin on amyloid processing and inflammatory response in TgCRND8 brain. Neurochem Res 2004 Oct; 29(10): 1897–911

    Article  PubMed  CAS  Google Scholar 

  77. Heneka MT, O’Banion MK. Inflammatory processes in Alzheimer’s disease. J Neuroimmunol 2007 Mar; 184(1-2): 69–91

    Article  PubMed  CAS  Google Scholar 

  78. Waldman A, Kritharides L. The pleiotropic effects of HMG-CoA reductase inhibitors: their role in osteoporosis and dementia. Drugs 2003; 63(2): 139–52

    Article  PubMed  CAS  Google Scholar 

  79. Ohm TG, Meske V. Cholesterol, statins and tau. Acta Neurol Scand Suppl 2006; 185: 93–101

    Article  PubMed  CAS  Google Scholar 

  80. Riekse RG, Li G, Petrie EC, et al. Effect of statins on Alzheimer’s disease biomarkers in cerebrospinal fluid. J Alzheimers Dis 2006 Dec; 10(4): 399–406

    PubMed  CAS  Google Scholar 

  81. Sparks DL, Sabbagh M, Connor D, et al. Statin therapy in Alzheimer’s disease. Acta Neurol Scand Suppl 2006; 185: 78–86

    Article  PubMed  CAS  Google Scholar 

  82. Zandi PP, Sparks DL, Khachaturian AS, et al. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch Gen Psychiatry 2005 Feb; 62(2): 217–24

    Article  PubMed  CAS  Google Scholar 

  83. Zhou B, Teramukai S, Fukushima M. Prevention and treatment of dementia or alzheimer’s disease by statins: a meta-analysis. Dement Geriatr Cogn Disord 2007 Jan 25; 23(3): 194–201

    Article  PubMed  CAS  Google Scholar 

  84. Albin RL. Parkinson’s disease: background, diagnosis, and initial management. Clin Geriatr Med 2006 Nov; 22(4): 735–51

    Article  PubMed  Google Scholar 

  85. McGeer PL, McGeer EG. Inflammation and neurodegeneration in Parkinson’s disease. Parkinsonism Relat Disord 2004 May; 10 Suppl. 1: S3–7

    Article  PubMed  Google Scholar 

  86. Sawada M, Imamura K, Nagatsu T. Role of cytokines in inflammatory process in Parkinson’s disease. J Neural Transm Suppl 2006; 70: 373–81

    Article  PubMed  CAS  Google Scholar 

  87. Mogi M, Harada M, Kondo T, et al. Interleukin-1 β, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett 1994 Oct 24; 180(2): 147–50

    Article  PubMed  CAS  Google Scholar 

  88. Wang Q, Wang PH, McLachlan C, et al. Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-inducedParkinsonian rats. Brain Res 2005 May 31; 1045(1-2): 229–33

    Article  PubMed  CAS  Google Scholar 

  89. Lieberman A, Lyons K, Levine J, et al. Statins, cholesterol, co-enzyme Q10, and Parkinson’s disease. Parkinsonism Relat Disord 2005 Mar; 11(2): 81–4

    Article  PubMed  Google Scholar 

  90. Somayajulu M, McCarthy S, Hung M, et al. Role of mitochondria in neuronal cell death induced by oxidative stress; neuroprotection by coenzyme Q10. Neurobiol Dis 2005 Apr; 18(3): 618–27

    Article  PubMed  CAS  Google Scholar 

  91. Huang X, Chen H, Miller WC, et al. Lower low-density lipo-protein cholesterol levels are associated with Parkinson’s disease. Mov Disord 2007 Feb 15; 22(3): 377–81

    Article  PubMed  Google Scholar 

  92. Ferguson B, Matyszak MK, Esiri MM, et al. Axonal damage in acute multiple sclerosis lesions. Brain 1997 Mar; 120(3): 393–9

    Article  PubMed  Google Scholar 

  93. Bar-Or A, Oliviera EML, Anderson DE, et al. Molecular patho-genesis of multiple sclerosis. J Neuroimmunol 1999 Dec; 100(1-2): 252–9

    Article  PubMed  CAS  Google Scholar 

  94. Freedman MS. Disease-modifying drugs for multiple sclerosis: current and future aspects. Expert Opin Pharmacother 2006 Oct;7 Suppl. 1: S1–9

    Article  PubMed  CAS  Google Scholar 

  95. Youssef S, Stuve O, Patarroyo JC, et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a TH2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 2002 Nov 7; 420(6911): 78–84

    Article  PubMed  CAS  Google Scholar 

  96. Vollmer T, Key L, Durkalski V, et al. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 2004 May 15; 363(9421): 1607–8

    Article  PubMed  CAS  Google Scholar 

  97. De Keyser J, Zeinstra E, Frohman E. Are astrocytes central players in the pathophysiology of multiple sclerosis? Arch Neurol 2003 Jan; 60(1): 132–6

    Article  PubMed  Google Scholar 

  98. Bo L, Mork S, Kong PA, et al. Detection of MHC class II-antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis lesions. J Neuroimmunol 1994 May; 51(2): 135–46

    Article  PubMed  CAS  Google Scholar 

  99. Ransohoff RM, Estes ML. Astrocyte expression of major his-tocompatibility complex gene products in multiple sclerosis brain tissue obtained by stereotactic biopsy. Arch Neurol 1991 Dec; 48(12): 1244–6

    Article  PubMed  CAS  Google Scholar 

  100. Zeinstra E, Wilczak N, Chesik D, et al. Simvastatin inhibits interferon-?-induced MHC class II up-regulation in cultured astrocytes. J Neuroinflammation 2006 Jul 21; 3: 16

    Article  PubMed  CAS  Google Scholar 

  101. Ifergan I, Wosik K, Cayrol R, et al. Statins reduce human blood-brain barrier permeability and restrict leukocyte migration: relevance to multiple sclerosis. Ann Neurol 2006 Jul; 60(1): 45–55

    Article  PubMed  CAS  Google Scholar 

  102. Ucar M, Mjorndal T, Dahlqvist R. HMG-CoA reductase inhibitors and myotoxicity. Drug Saf 2000 Jun; 22(6): 441–57

    Article  PubMed  CAS  Google Scholar 

  103. Christopher-Stine L. Statin myopathy: an update. Curr Opin Rheumatol 2006 Nov; 18(6): 647–53

    PubMed  CAS  Google Scholar 

  104. Ballantyne CM, Corsini A, Davidson MH, et al. Risk for myopathy with statin therapy in high-risk patients. Arch Intern Med 2003 Mar 10; 163(5): 553–64

    Article  PubMed  CAS  Google Scholar 

  105. Mukhtar RY, Reckless JP. Statin-induced myositis: a commonly encountered or rare side effect? Curr Opin Lipidol 2005 Dec; 16(6): 640–7

    PubMed  CAS  Google Scholar 

  106. Chasman DI, Posada D, Subrahmanyan L, et al. Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA 2004 Jun 16; 291(23): 2821–7

    Article  PubMed  CAS  Google Scholar 

  107. Jamal SM, Eisenberg MJ, Christopoulos S. Rhabdomyolysis associated with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am Heart J 2004 Jun; 147(6): 956–65

    Article  PubMed  CAS  Google Scholar 

  108. Farmer JA, Torre-Amione G. Comparative tolerability of the HMG-CoA reductase inhibitors. Drug Saf 2000 Sep; 23(3): 197–213

    Article  PubMed  CAS  Google Scholar 

  109. Gershovich OE, Lyman Jr AE. Liver function test abnormalities and pruritus in a patient treated with atorvastatin: case report and review of the literature. Pharmacotherapy 2004 Jan; 24(1): 150–4

    Article  PubMed  Google Scholar 

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  1. SUNY Stony Brook School of Medicine, Vascular Biology Institute, Winthrop-University Hospital, 222 Station Plaza, North, Suite 511-A, Mineola, New York, 11501, USA

    Allison B. Reiss

  2. Division of Neurology, Department of Medicine, Winthrop-University Hospital, Mineola, New York, USA

    Elzbieta Wirkowski

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Reiss, A.B., Wirkowski, E. Role of HMG-CoA Reductase Inhibitors in Neurological Disorders. Drugs 67, 2111–2120 (2007). https://doi.org/10.2165/00003495-200767150-00001

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