Cholesterol-independent neuroprotective and neurotoxic activities of statins: Perspectives for statin use in Alzheimer disease and other age-related neurodegenerative disorders

被引：73
作者：
Butterfield, D. Allan [1 ,2 ]
Barone, Eugenio [3 ]
Mancuso, Cesare [3 ]
机构：
[1] Univ Kentucky, Dept Chem, Ctr Membrane Sci, Lexington, KY 40506 USA
[2] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40506 USA
[3] Catholic Univ, Sch Med, Inst Pharmacol, I-00168 Rome, Italy
来源：
PHARMACOLOGICAL RESEARCH | 2011年 / 64卷 / 03期
关键词：
Statins; Pleiotropic functions; Alzheimer disease; Statins as Janus molecules; COA REDUCTASE INHIBITORS; NITRIC-OXIDE SYNTHASE; MILD COGNITIVE IMPAIRMENT; CLINICAL-TRIAL COHORT; OXIDATIVE STRESS; DRUG-INTERACTIONS; COENZYME Q(10); AMYLOID-BETA; CELL-DEATH; AUTOIMMUNE-DISEASE;
D O I：
10.1016/j.phrs.2011.04.007
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Statins, long known to be beneficial in conditions where dyslipidemia occurs by lowering serum cholesterol levels, also have been proposed for use in neurodegenerative conditions, including Alzheimer disease. However, it is not clear that the purported effectiveness of statins in neurodegenerative disorders is directly related to cholesterol-lowering effects of these agents; rather, the pleiotropic functions of statins likely play critical roles. Moreover, it is becoming more apparent with additional studies that statins can have deleterious effects in preclinical studies and lack effectiveness in various recent clinical trials. This perspective paper outlines pros and cons of the use of statins in neurodegenerative disorders, with particular emphasis on Alzheimer disease. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：180 / 186
页数：7
相关论文
共 99 条
  • [81] Reduced risk of incident AD with elective statin use in a clinical trial cohort
    Sparks, D. Larry
    Kryscio, Richard J.
    Sabbagh, Marwan N.
    Connor, Donald J.
    Sparks, Lisa M.
    Liebsack, Carolyn
    [J]. CURRENT ALZHEIMER RESEARCH, 2008, 5 (04) : 416 - 421
  • [82] Cholesterol and Cognitive Performance in Normal Controls and the Influence of Elective Statin Use after Conversion to Mild Cognitive Impairment: Results in a Clinical Trial Cohort
    Sparks, D. Larry
    Kryscio, Richard J.
    Connor, Donald J.
    Sabbagh, Marwan N.
    Sparks, Lisa M.
    Lin, Yushun
    Liebsack, Carolyn
    [J]. NEURODEGENERATIVE DISEASES, 2010, 7 (1-3) : 183 - 186
  • [83] Stump AL, 2006, AM FAM PHYSICIAN, V74, P605
  • [84] Redox Proteomic Analysis of Carbonylated Brain Proteins in Mild Cognitive Impairment and Early Alzheimer's Disease
    Sultana, Rukhsana
    Perluigi, Marzia
    Newman, Shelley F.
    Pierce, William M.
    Cini, Chiara
    Coccia, Raffaella
    Butterfield, D. Allan
    [J]. ANTIOXIDANTS & REDOX SIGNALING, 2010, 12 (03) : 327 - 336
  • [85] Oxidatively modified proteins in Alzheimer's disease (AD), mild cognitive impairment and animal models of AD: role of Abeta in pathogenesis
    Sultana, Rukhsana
    Perluigi, Marzia
    Butterfield, D. Allan
    [J]. ACTA NEUROPATHOLOGICA, 2009, 118 (01) : 131 - 150
  • [86] Regulation of reactive-oxygen-species generation in fibroblasts by Rac1
    Sundaresan, M
    Yu, ZX
    Ferrans, VJ
    Sulciner, DJ
    Gutkind, JS
    Irani, K
    GoldschmidtClermont, PJ
    Finkel, T
    [J]. BIOCHEMICAL JOURNAL, 1996, 318 : 379 - 382
  • [87] High-dose statin treatment does not alter plasma marker for brain cholesterol metabolism in patients with moderately elevated plasma cholesterol levels
    Thelen, Karin M.
    Laaksonen, Reijo
    Paiva, Hann
    Lehtimaki, Terho
    Lutjohann, Dieter
    [J]. JOURNAL OF CLINICAL PHARMACOLOGY, 2006, 46 (07) : 812 - 816
  • [88] Simvastatin improves cerebrovascular function and counters soluble amyloid-beta, inflammation and oxidative stress in aged APP mice
    Tong, Xin-Kang
    Nicolakakis, Nektaria
    Fernandes, Priscilla
    Ongali, Brice
    Brouillette, Jonathan
    Quirion, Remi
    Hamel, Edith
    [J]. NEUROBIOLOGY OF DISEASE, 2009, 35 (03) : 406 - 414
  • [89] Pravastatin and cognitive function in the elderly. Results of the PROSPER study
    Trompet, Stella
    van Vliet, Peter
    de Craen, Anton J. M.
    Jolles, Jelle
    Buckley, Brendan M.
    Murphy, Michael B.
    Ford, Ian
    Macfarlane, Peter W.
    Sattar, Naveed
    Packard, Chris J.
    Stott, David J.
    Shepherd, Jim
    Bollen, Eduard L. E. M.
    Blauw, Gerard J.
    Jukema, J. Wouter
    Westendorp, Rudi G. J.
    [J]. JOURNAL OF NEUROLOGY, 2010, 257 (01) : 85 - 90
  • [90] 25-hydroxycholesterol provokes oligodendrocyte cell line apoptosis and stimulates the secreted phospholipase A2 type IIA via LXR beta and PXR
    Trousson, Amalia
    Bernard, Sophie
    Petit, Patrice X.
    Liere, Philippe
    Pianos, Antoine
    El Hadri, Khadija
    Lobaccaro, Jean-Marc A.
    Ghandour, M. Said
    Raymondjean, Michel
    Schumacher, Michael
    Massaad, Charbel
    [J]. JOURNAL OF NEUROCHEMISTRY, 2009, 109 (04) : 945 - 958
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