Prospects of statins in Parkinson disease.
Parkinson disease (PD) is second only to Alzheimer disease as the most common neurodegenerative disorder in humans. Despite intense investigations, no effective therapy is available to halt the progression of PD. Although statins are widely used cholesterol-lowering drugs throughout the world, recent studies suggest that these drugs modulate neurodegeneration-related signaling processes and may be beneficial for PD. Simvastatin is the most potent statin in crossing the blood-brain barrier, and this particular statin drug negatively correlates with the incidence of PD and shows efficacy in animal models of PD. However, PD mainly occurs in the aging population, who are more vulnerable to cholesterol or lipid-related disorders, raising questions whether this possible beneficial effect of statins in PD patients is cholesterol dependent or cholesterol independent. This article presents data on the therapeutic efficacy of simvastatin in a chronic MPTP model of PD, reviews recent literature, and discusses the pros and cons of statin therapy in PD.
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA.
Avik
A
Roy
Kalipada
K
Pahan
D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
Brain Res. 2005 Mar 10;1037(1-2):1-6
15777746
Pharmacol Res. 2009 Jul;60(1):41-5
19427584
J Leukoc Biol. 2007 Nov;82(5):1083-94
17675560
Proc Natl Acad Sci U S A. 2003 May 13;100(10):6145-50
12721370
J Neurochem. 2000 Jun;74(6):2288-95
10820188
Nature. 1999 Jun 10;399(6736):597-601
10376602
Eur J Biochem. 1977 Jul 1;77(1):31-6
908337
FASEB J. 2003 Oct;17(13):1954-6
12897068
J Neurosci Res. 2003 Apr 15;72(2):141-6
12671988
Neurology. 2008 Apr 15;70(16 Pt 2):1418-22
18184918
Cell Death Differ. 1999 Oct;6(10):964-8
10556973
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14524-9
12376616
J Biol Chem. 1998 Jan 30;273(5):2591-600
9446561
J Neurochem. 2010 Sep 1;114(5):1261-76
20524958
Ann N Y Acad Sci. 2010 Jun;1199:69-76
20633110
Cell. 2009 Apr 3;137(1):47-59
19345186
J Neurosci. 2008 Apr 23;28(17):4311-6
18434508
Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9435-40
15197276
J Antibiot (Tokyo). 1976 Dec;29(12):1346-8
1010803
Exp Neurol. 2011 Jul;230(1):27-34
20406638
Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10813-8
12122208
Mov Disord. 2003 Feb;18(2):121-9
12539204
J Am Coll Cardiol. 2003 Aug 20;42(4):690-7
12932603
BMC Med. 2007 Jul 19;5:20
17640385
Biochemistry. 2010 Jul 6;49(26):5426-35
20521763
Mov Disord. 2007 Feb 15;22(3):377-81
17177184
Nat Med. 2004 Jul;10 Suppl:S58-62
15272270
J Immunol. 2010 Feb 15;184(4):1799-809
20083653
Parkinsonism Relat Disord. 2008;14 Suppl 2:S112-5
18585085
Trans Assoc Am Physicians. 1983;96:1-9
6388097
Biol Psychiatry. 2007 Oct 1;62(7):800-10
17662258
Science. 2000 Feb 18;287(5456):1265-9
10678833
FASEB J. 2006 Apr;20(6):670-82
16581975
Trends Biochem Sci. 2003 Sep;28(9):502-8
13678962
J Neurosci. 2009 Oct 28;29(43):13543-56
19864567
Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18754-9
18000063
Biochem Med Metab Biol. 1993 Apr;49(2):133-42
8484956
Drugs Today (Barc). 2003 Feb;39(2):137-43
12698208
Cardiovasc Res. 2003 Jan;57(1):253-64
12504836
Neurology. 2004 Jun 22;62(12):2198-202
15210882
J Neurosci. 2001 Dec 15;21(24):9549-60
11739566
J Clin Invest. 1998 Jun 15;101(12):2711-9
9637705
PLoS One. 2008 Jan 02;3(1):e1376
18167537
Arch Intern Med. 2003 Sep 8;163(16):1926-32
12963565
J Lipid Res. 1980 Jul;21(5):505-17
6995544
Circulation. 2001 Jan 2;103(1):113-8
11136695
Trends Pharmacol Sci. 2003 Aug;24(8):395-401
12915048
Biomed Pharmacother. 1999 Apr;53(3):141-5
10349502
Brain Res. 2007 Mar 2;1135(1):77-84
17196944
Neurology. 2008 May 20;70(21):1972-9
18401018
J Immunol. 2009 Aug 1;183(3):2045-58
19587012
Nat Chem Biol. 2006 May;2(5):249-53
16565714
J Clin Invest. 1997 Dec 1;100(11):2671-9
9389730
J Neurochem. 2000 May;74(5):2213-6
10800968
J Neurosci Res. 2004 May 15;76(4):563-71
15114628
Am J Nephrol. 2004 Nov-Dec;24(6):606-13
15583480
Neuroscience. 1996 May;72(2):355-63
8737406
J Neurochem. 2008 Jun;105(5):1656-67
18248604
Biochem Biophys Res Commun. 2006 Mar 24;341(4):1088-95
16460685
Am J Epidemiol. 2006 Nov 15;164(10):998-1002
16905642
J Neurosci. 2002 Jun 15;22(12):5042-54
12077200
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7531-6
9207126
J Biol Chem. 1999 Nov 19;274(47):33644-53
10559253
Neuroreport. 1995 Aug 21;6(12):1642-4
8527732
Neurobiol Dis. 2005 Dec;20(3):898-906
16006134
J Am Soc Nephrol. 2003 May;14(5):1336-48
12707403
FASEB J. 2006 Oct;20(12):2000-8
17012252
Neuron. 2003 Sep 11;39(6):889-909
12971891
Parkinsonism Relat Disord. 2009 Dec;15 Suppl 4:S8-12
20123563
Blood. 2006 May 1;107(9):3632-8
16397128
Dement Geriatr Cogn Disord. 2006;22(5-6):392-8
16960448
Annu Rev Neurosci. 1999;22:123-44
10202534
Exp Neurol. 2010 Feb;221(2):267-74
19944097