Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

The Effect of Statins on the Differentiation and Function of Central Nervous System Cells

Author(s): Sajjad Chamani, Leila Mobasheri, Shadi Zerehpoosh, Ali Naghizadeh, Alice P. McCloskey, Manfredi Rizzo, Tannaz Jamialahmadi and Amirhossein Sahebkar*

Volume 31, Issue 11, 2024

Published on: 12 May, 2023

Page: [1348 - 1360] Pages: 13

DOI: 10.2174/0929867330666230308121645

Price: $65

Open Access Journals Promotions 2
conference banner
Abstract

Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) reduce plasma cholesterol and improve endothelium-dependent vasodilation, inflammation, and oxidative stress. The effect of statins on the central nervous system (CNS), particularly on cognition and neurological disorders such as cerebral ischemic stroke, multiple sclerosis (MS), and Alzheimer’s disease (AD), has received increasing attention in recent years, both within the scientific community and in the media. This review aims to provide an updated discussion on the effects of statins on the differentiation and function of various nervous system cells, including neurons and glial cells. Additionally, the mechanisms of action and how different types of statins enter the CNS will be discussed.

Keywords: Statins, neurodegeneration, pleiotropic effect, central nervous system, inflammation, plasma cholesterol.

« Previous Next »
[1]
Saku, K.; Zhang, B.; Noda, K. Randomized head-to-head comparison of pitavastatin, atorvastatin, and rosuvastatin for safety and efficacy (quantity and quality of LDL): the PATROL trial. Circ. J., 2011, 75(6), 1493-1505.
[http://dx.doi.org/10.1253/circj.CJ-10-1281] [PMID: 21498906]
[2]
Meor Anuar Shuhaili, M.F.R.; Samsudin, I.N.; Stanslas, J.; Hasan, S.; Thambiah, S.C. Effects of different types of statins on lipid profile: A perspective on Asians. Int. J. Endocrinol. Metab., 2017, e43319.
[http://dx.doi.org/10.5812/ijem.43319] [PMID: 28848611]
[3]
Welty, F.K.; Lewis, S.J.; Friday, K.E.; Cain, V.A.; Anzalone, D.A. A comparison of statin therapies in hypercholesterolemia in women: A subgroup analysis of the STELLAR study. J. Womens Health (Larchmt.), 2016, 25(1), 50-56.
[http://dx.doi.org/10.1089/jwh.2015.5271] [PMID: 26539650]
[4]
Taylor, F.; Huffman, M.D.; Macedo, A.F.; Moore, T.H.; Burke, M.; Davey Smith, G.; Ward, K.; Ebrahim, S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst. Rev., 2013, 2013(1), CD004816.
[PMID: 23440795]
[5]
Saeedi Saravi, S.S.; Saeedi Saravi, S.S.; Arefidoust, A.; Dehpour, A.R. The beneficial effects of HMG-CoA reductase inhibitors in the processes of neurodegeneration. Metab. Brain Dis., 2017, 32(4), 949-965.
[http://dx.doi.org/10.1007/s11011-017-0021-5] [PMID: 28578514]
[6]
Bahrami, A.; Parsamanesh, N.; Atkin, S.L.; Banach, M.; Sahebkar, A. Effect of statins on toll-like receptors: A new insight to pleiotropic effects. Pharmacol. Res., 2018, 135, 230-238.
[http://dx.doi.org/10.1016/j.phrs.2018.08.014] [PMID: 30120976]
[7]
Ferretti, G.; Bacchetti, T.; Sahebkar, A. Effect of statin therapy on paraoxonase-1 status: A systematic review and meta-analysis of 25 clinical trials. Prog. Lipid Res., 2015, 60, 50-73.
[http://dx.doi.org/10.1016/j.plipres.2015.08.003] [PMID: 26416579]
[8]
Khalifeh, M.; Penson, P.; Banach, M.; Sahebkar, A. Statins as anti-pyroptotic agents. Arch. Med. Sci., 2021, 17(5), 1414-1417.
[http://dx.doi.org/10.5114/aoms/141155] [PMID: 34522271]
[9]
Kouhpeikar, H.; Delbari, Z.; Sathyapalan, T.; Simental-Mendía, L.E.; Jamialahmadi, T.; Sahebkar, A. The effect of statins through mast cells in the pathophysiology of atherosclerosis: A review. Curr. Atheroscler. Rep., 2020, 22(5), 19.
[http://dx.doi.org/10.1007/s11883-020-00837-9] [PMID: 32458165]
[10]
Parizadeh, S.M.R.; Azarpazhooh, M.R.; Moohebati, M.; Nematy, M.; Ghayour-Mobarhan, M.; Tavallaie, S.; Rahsepar, A.A.; Amini, M.; Sahebkar, A.; Mohammadi, M.; Ferns, G.A.A. Simvastatin therapy reduces prooxidant-antioxidant balance: Results of a placebo-controlled cross-over trial. Lipids, 2011, 46(4), 333-340.
[http://dx.doi.org/10.1007/s11745-010-3517-x] [PMID: 21207250]
[11]
Shakour, N.; Ruscica, M.; Hadizadeh, F.; Cirtori, C.; Banach, M.; Jamialahmadi, T.; Sahebkar, A. Statins and C-reactive protein: In silico evidence on direct interaction. Arch. Med. Sci., 2020, 16(6), 1432-1439.
[http://dx.doi.org/10.5114/aoms.2020.100304] [PMID: 33224343]
[12]
Sahebkar, A.; Chew, G.T.; Watts, G.F. Recent advances in pharmacotherapy for hypertriglyceridemia. Prog. Lipid Res., 2014, 56, 47-66.
[http://dx.doi.org/10.1016/j.plipres.2014.07.002] [PMID: 25083925]
[13]
Lashgari N.A., Roudsari N.M., Zadeh S.S.T., Momtaz S., Abbasifard M., Reiner Ž., Abdolghaffari A.H., Sahebkar A. Statins block mammalian target of rapamycin pathway: a possible novel therapeutic strategy for inflammatory, malignant and neurodegenerative diseases. Inflammopharmacology. 2023 Feb;31(1):57-75. http://dx.doi.org/10.1007/ s10787-022-01077-w. Epub 2022 Dec 27. PMID: 36574095; PMCID: PMC9792946.
[14]
Bland, A.R.; Payne, F.M.; Ashton, J.C.; Jamialahmadi, T.; Sahebkar, A. The cardioprotective actions of statins in targeting mitochondrial dysfunction associated with myocardial ischaemia-reperfusion injury. Pharmacol. Res., 2022, 175, 105986.
[http://dx.doi.org/10.1016/j.phrs.2021.105986] [PMID: 34800627]
[15]
Chruściel, P.; Sahebkar, A.; Rembek-Wieliczko, M.; Serban, M.C.; Ursoniu, S.; Mikhailidis, D.P.; Jones, S.R.; Mosteoru, S.; Blaha, M.J.; Martin, S.S.; Rysz, J.; Toth, P.P.; Lip, G.Y.H.; Pencina, M.J.; Ray, K.K.; Banach, M. Impact of statin therapy on plasma adiponectin concentrations: A systematic review and meta-analysis of 43 randomized controlled trial arms. Atherosclerosis, 2016, 253, 194-208.
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.07.897] [PMID: 27498397]
[16]
Dehnavi, S.; Kiani, A.; Sadeghi, M.; Biregani, A.F.; Banach, M.; Atkin, S.L.; Jamialahmadi, T.; Sahebkar, A. Targeting AMPK by statins: A potential therapeutic approach. Drugs, 2021, 81(8), 923-933.
[http://dx.doi.org/10.1007/s40265-021-01510-4] [PMID: 33939118]
[17]
Gorabi, A.M.; Kiaie, N.; Bianconi, V.; Pirro, M.; Jamialahmadi, T.; Sahebkar, A. Statins attenuate fibrotic manifestations of cardiac tissue damage. Curr. Mol. Pharmacol., 2021, 14(5), 782-797.
[http://dx.doi.org/10.2174/1874467214666210210123206] [PMID: 33568040]
[18]
Sahebkar, A.; Kotani, K.; Serban, C.; Ursoniu, S.; Mikhailidis, D.P.; Jones, S.R.; Ray, K.K.; Blaha, M.J.; Rysz, J.; Toth, P.P.; Muntner, P.; Lip, G.Y.H.; Banach, M. Statin therapy reduces plasma endothelin-1 concentrations: A meta-analysis of 15 randomized controlled trials. Atherosclerosis, 2015, 241(2), 433-442.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.05.022] [PMID: 26074317]
[19]
Sahebkar, A.; Serban, C.; Mikhailidis, D.P.; Undas, A.; Lip, G.Y.H.; Muntner, P.; Bittner, V.; Ray, K.K.; Watts, G.F.; Hovingh, G.K.; Rysz, J.; Kastelein, J.J.; Banach, M. Association between statin use and plasma D-dimer levels. A systematic review and meta-analysis of randomised controlled trials. Thromb. Haemost., 2015, 114(3), 546-557.
[PMID: 26017749]
[20]
Serban, C.; Sahebkar, A.; Ursoniu, S.; Mikhailidis, D.P.; Rizzo, M.; Lip, G.Y.H.; Kees Hovingh, G.; Kastelein, J.J.P.; Kalinowski, L.; Rysz, J.; Banach, M. A systematic review and meta-analysis of the effect of statins on plasma asymmetric dimethylarginine concentrations. Sci. Rep., 2015, 5(1), 9902.
[http://dx.doi.org/10.1038/srep09902] [PMID: 25970700]
[21]
Sohrevardi, S.; Nasab, F.; Mirjalili, M.; Bagherniya, M.; Tafti, A.; Jarrahzadeh, M.; Azarpazhooh, M.; Saeidmanesh, M.; Banach, M.; Jamialahmadi, T.; Sahebkar, A. Effect of atorvastatin on delirium status of patients in the intensive care unit: a randomized controlled trial. Arch. Med. Sci., 2019, 17(5), 1423-1428.
[http://dx.doi.org/10.5114/aoms.2019.89330] [PMID: 34522273]
[22]
Koushki K, Shahbaz SK, Mashayekhi K, Sadeghi M, Zayeri ZD, Taba MY, Banach M, Al-Rasadi K, Johnston TP, Sahebkar A. Anti-inflammatory action of statins in cardiovascular disease: the role of inflammasome and toll-like receptor pathways. Clin Rev Allergy Immunol.2021 Apr; 60(2):175-199. http://dx.doi.org/10.1007/s12016-020-08791-9. PMID: 32378144; PMCID: PMC7985098.
[23]
(a) ) Bahrami, A.; Bo, S.; Jamialahmadi, T.; Sahebkar, A. Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on ageing: Molecular mechanisms. Ageing Res. Rev., 2020, 58, 101024. http://dx.doi.org/10.1016/j.arr.2020.101024 PMID: 32006687 (b) Ward NC, Watts GF, Eckel RH. Statin toxicity. Circ Res., 2019 Jan 18; 124(2), 328-350 http://dx.doi.org/10.1161/CIRCRESAHA.118.312782 PMID: 30653440 (c) Attardo S, Musumeci O, Velardo D, Toscano A. Statins neuromuscular adverse effects. Int J Mol Sci. 2022 Jul 28; 23(15):8364. http://dx.doi.org/10.3390/ijms23158364. PMID: 35955495; PMCID: PMC936917 (d) Banach, M.; Serban, C.; Ursoniu, S.; Rysz, J.; Muntner, P.; Toth, P.P.; Jones, S.R.; Rizzo, M.; Glasser, S.P.; Watts, G.F.; Blumenthal, R.S.; Lip, G.Y.H.; Mikhailidis, D.P.; Sahebkar, A. Statin therapy and plasma coenzyme Q10 concentrations-a systematic review and meta-analysis of placebo controlled trials. Pharmacol. Res., 2015, 99, 329-336. http://dx.doi.org/10.1016/j.phrs.2015.07.008 PMID: 26192349
[24]
Zhang, Q.; Dong, J.; Yu, Z. Pleiotropic use of Statins as non-lipid-lowering drugs. Int. J. Biol. Sci., 2020, 16(14), 2704-2711.
[http://dx.doi.org/10.7150/ijbs.42965] [PMID: 33110390]
[25]
Gorabi, A.M.; Kiaie, N.; Hajighasemi, S.; Banach, M.; Penson, P.E.; Jamialahmadi, T.; Sahebkar, A. Statin-induced nitric oxide signaling: Mechanisms and therapeutic implications. J. Clin. Med., 2019, 8(12), 2051.
[http://dx.doi.org/10.3390/jcm8122051] [PMID: 31766595]
[26]
Zhou, J.; Cheng, M.; Liao, Y.H.; Hu, Y.; Wu, M.; Wang, Q.; Qin, B.; Wang, H.; Zhu, Y.; Gao, X.M.; Goukassian, D.; Zhao, T.C.; Tang, Y.L.; Kishore, R.; Qin, G. Rosuvastatin enhances angiogenesis via eNOS-dependent mobilization of endothelial progenitor cells. PLoS One, 2013, 8(5), e63126.
[http://dx.doi.org/10.1371/journal.pone.0063126] [PMID: 23704894]
[27]
Bonetti, P.; Lerman, L.O.; Napoli, C.; Lerman, A. Statin effects beyond lipid lowering-are they clinically relevant? Eur. Heart J., 2003, 24(3), 225-248.
[http://dx.doi.org/10.1016/S0195-668X(02)00419-0] [PMID: 12590901]
[28]
Liao, J.K.; Laufs, U. Pleiotropic effects of statins. Annu. Rev. Pharmacol. Toxicol., 2005, 45(1), 89-118.
[http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.095748] [PMID: 15822172]
[29]
Sadowitz, B.; Maier, K.G.; Gahtan, V. Basic science review: Statin therapy-Part I: The pleiotropic effects of statins in cardiovascular disease. Vasc. Endovascular Surg., 2010, 44(4), 241-251.
[http://dx.doi.org/10.1177/1538574410362922] [PMID: 20403949]
[30]
Zhou, Q.; Liao, J.K. Pleiotropic effects of statins. Basic research and clinical perspectives -. Circ. J., 2010, 74(5), 818-826.
[http://dx.doi.org/10.1253/circj.CJ-10-0110] [PMID: 20424337]
[31]
Climent, E.; Benaiges, D.; Pedro-Botet, J. Hydrophilic or lipophilic statins? Front. Cardiovasc. Med., 2021, 8, 687585.
[http://dx.doi.org/10.3389/fcvm.2021.687585] [PMID: 34095267]
[32]
Kim, M.C.; Ahn, Y.; Jang, S.Y.; Cho, K.H.; Hwang, S.H.; Lee, M.G.; Ko, J.S.; Park, K.H.; Sim, D.S.; Yoon, N.S.; Yoon, H.J.; Kim, K.H.; Hong, Y.J.; Park, H.W.; Kim, J.H.; Jeong, M.H.; Cho, J.G.; Park, J.C.; Kang, J.C. Comparison of clinical outcomes of hydrophilic and lipophilic statins in patients with acute myocardial infarction. Korean J. Intern. Med. (Korean. Assoc. Intern. Med.), 2011, 26(3), 294-303.
[http://dx.doi.org/10.3904/kjim.2011.26.3.294] [PMID: 22016590]
[33]
Bonsu, K.O.; Kadirvelu, A.; Reidpath, D.D. Lipophilic versus hydrophilic statin therapy for heart failure: a protocol for an adjusted indirect comparison meta-analysis. Syst. Rev., 2013, 2(1), 22.
[http://dx.doi.org/10.1186/2046-4053-2-22] [PMID: 23618535]
[34]
Hopkins, WGLD rowth and Differentiation of the Nervous System. Anim Sci., 2018.
[35]
Wood, W.G.; Eckert, G.P.; Igbavboa, U.; Müller, W.E. Statins and neuroprotection. Ann. N. Y. Acad. Sci., 2010, 1199(1), 69-76.
[http://dx.doi.org/10.1111/j.1749-6632.2009.05359.x] [PMID: 20633110]
[36]
Lütjohann, D.; Stroick, M.; Bertsch, T.; Kühl, S.; Lindenthal, B.; Thelen, K.; Andersson, U.; Björkhem, I.; Bergmann, K.; Fassbender, K. High doses of simvastatin, pravastatin, and cholesterol reduce brain cholesterol synthesis in guinea pigs. Steroids, 2004, 69(6), 431-438.
[http://dx.doi.org/10.1016/j.steroids.2004.03.012] [PMID: 15219793]
[37]
Johnson-Anuna, L.N.; Eckert, G.P.; Keller, J.H.; Igbavboa, U.; Franke, C.; Fechner, T.; Schubert-Zsilavecz, M.; Karas, M.; Müller, W.E.; Wood, W.G. Chronic administration of statins alters multiple gene expression patterns in mouse cerebral cortex. J. Pharmacol. Exp. Ther., 2005, 312(2), 786-793.
[http://dx.doi.org/10.1124/jpet.104.075028] [PMID: 15358814]
[38]
Puglielli, L.; Tanzi, R.E.; Kovacs, D.M. Alzheimer’s disease: The cholesterol connection. Nat. Neurosci., 2003, 6(4), 345-351.
[http://dx.doi.org/10.1038/nn0403-345] [PMID: 12658281]
[39]
Menge, T.; Hartung, H.P.; Stüve, O. Statins-a cure-all for the brain? Nat. Rev. Neurosci., 2005, 6(4), 325-331.
[http://dx.doi.org/10.1038/nrn1652] [PMID: 15803163]
[40]
Amarenco, P.; Tonkin, A.M. Statins for stroke prevention: Disappointment and hope. Circulation, 2004, 109(23_suppl_1)(Suppl. 1), III44-III49.
[http://dx.doi.org/10.1161/01.CIR.0000131518.25959.8F] [PMID: 15198966]
[41]
Briel, M.; Studer, M.; Glass, T.R.; Bucher, H.C. Effects of statins on stroke prevention in patients with and without coronary heart disease: A meta-analysis of randomized controlled trials. Am. J. Med., 2004, 117(8), 596-606.
[http://dx.doi.org/10.1016/j.amjmed.2004.04.022] [PMID: 15465509]
[42]
Sever, P.S.; Dahlöf, B.; Poulter, N.R.; Wedel, H.; Beevers, G.; Caulfield, M.; Collins, R.; Kjeldsen, S.E.; Kristinsson, A.; McInnes, G.T.; Mehlsen, J.; Nieminen, M.; O’Brien, E.; Östergren, J. 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, 361(9364), 1149-1158.
[http://dx.doi.org/10.1016/S0140-6736(03)12948-0] [PMID: 12686036]
[43]
Corder, E.H.; Saunders, A.M.; Strittmatter, W.J.; Schmechel, D.E.; Gaskell, P.C.; Small, G.W.; Roses, A.D.; Haines, J.L.; Pericak-Vance, M.A. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science, 1993, 261(5123), 921-923.
[http://dx.doi.org/10.1126/science.8346443] [PMID: 8346443]
[44]
Miserez, AR Alzheimer dementia-a disorder of lipoprotein metabolism?. Praxis (Bern 1994)., 2001, 90(31-32), 1297-9.
[45]
Geifman, N.; Brinton, R.D.; Kennedy, R.E.; Schneider, L.S.; Butte, A.J. Evidence for benefit of statins to modify cognitive decline and risk in Alzheimer’s disease. Alzheimers Res. Ther., 2017, 9(1), 10.
[http://dx.doi.org/10.1186/s13195-017-0237-y] [PMID: 28212683]
[46]
Huang, C-N.; Li, H-H.; Lin, C-L. Neuroprotective effects of statins against amyloid β-induced neurotoxicity. Neural Regen. Res., 2018, 13(2), 198-206.
[http://dx.doi.org/10.4103/1673-5374.226379] [PMID: 29557360]
[47]
Griffin, J.M.; Kho, D.; Graham, E.S.; Nicholson, L.F.B.; O’Carroll, S.J. Statins inhibit fibrillary β-amyloid induced inflammation in a model of the human blood brain barrier. PLoS One, 2016, 11(6), e0157483.
[http://dx.doi.org/10.1371/journal.pone.0157483] [PMID: 27309956]
[48]
Vollmer, T.; Key, L.; Durkalski, V.; Tyor, W.; Corboy, J.; Markovic-Plese, S.; Preiningerova, J.; Rizzo, M.; Singh, I. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet, 2004, 363(9421), 1607-1608.
[http://dx.doi.org/10.1016/S0140-6736(04)16205-3] [PMID: 15145635]
[49]
Domoki, F.; Kis, B.; Gáspár, T.; Snipes, J.A.; Bari, F.; Busija, D.W. Rosuvastatin induces delayed preconditioning against l-glutamate excitotoxicity in cultured cortical neurons. Neurochem. Int., 2010, 56(3), 404-409.
[http://dx.doi.org/10.1016/j.neuint.2009.11.013] [PMID: 19931334]
[50]
Fairless, R.; Bading, H.; Diem, R. Pathophysiological ionotropic glutamate signalling in neuroinflammatory disease as a therapeutic target. Front. Neurosci., 2021, 15, 741280.
[http://dx.doi.org/10.3389/fnins.2021.741280] [PMID: 34744612]
[51]
Carson, R.A.; Rudine, A.C.; Tally, S.J.; Franks, A.L.; Frahm, K.A.; Waldman, J.K.; Silswal, N.; Burale, S.; Phan, J.V.; Chandran, U.R.; Monaghan, A.P.; DeFranco, D.B. Statins impact primary embryonic mouse neural stem cell survival, cell death, and fate through distinct mechanisms. PLoS One, 2018, 13(5), e0196387.
[http://dx.doi.org/10.1371/journal.pone.0196387] [PMID: 29738536]
[52]
Pavlov, O.V.; Bobryshev, Y.V.; Balabanov, Y.V.; Ashwell, K. An in vitro study of the effects of lovastatin on human fetal brain cells. Neurotoxicol. Teratol., 1995, 17(1), 31-39.
[http://dx.doi.org/10.1016/0892-0362(95)91641-W] [PMID: 7708017]
[53]
Mauch, D.H.; Nägler, K.; Schumacher, S.; Göritz, C.; Müller, E.C.; Otto, A.; Pfrieger, F.W. CNS synaptogenesis promoted by glia-derived cholesterol. Science, 2001, 294(5545), 1354-1357.
[http://dx.doi.org/10.1126/science.294.5545.1354] [PMID: 11701931]
[54]
Jeppesen, U.; Gaist, D.; Smith, T.; Sindrup, S. Statins and peripheral neuropathy. Eur J Clin Pharmacol., 1999, 54(11), 835-8.
[http://dx.doi.org/10.1007/s002280050562]
[55]
Gaist, D.; Jeppesen, U.; Andersen, M.; García Rodríguez, L.A.; Hallas, J.; Sindrup, S.H. Statins and risk of polyneuropathy: A case-control study. Neurology, 2002, 58(9), 1333-1337.
[http://dx.doi.org/10.1212/WNL.58.9.1333] [PMID: 12011277]
[56]
Muldoon, M.F.; Manuck, S.B.; Mendelsohn, A.B.; Kaplan, J.R.; Belle, S.H. Cholesterol reduction and non-illness mortality: Meta-analysis of randomised clinical trials. BMJ, 2001, 322(7277), 11-15.
[http://dx.doi.org/10.1136/bmj.322.7277.11] [PMID: 11141142]
[57]
Wagstaff, L.R.; Mitton, M.W.; Arvik, B.M.; Doraiswamy, P.M. Statin-associated memory loss: Analysis of 60 case reports and review of the literature. Pharmacotherapy, 2003, 23(7), 871-880.
[http://dx.doi.org/10.1592/phco.23.7.871.32720] [PMID: 12885101]
[58]
Kotti, T.J.; Ramirez, D.M.O.; Pfeiffer, B.E.; Huber, K.M.; Russell, D.W. Brain cholesterol turnover required for geranylgeraniol production and learning in mice. Proc. Natl. Acad. Sci. USA, 2006, 103(10), 3869-3874.
[http://dx.doi.org/10.1073/pnas.0600316103] [PMID: 16505352]
[59]
März, P.; Otten, U.; Miserez, A.R. Statins induce differentiation and cell death in neurons and astroglia. Glia, 2007, 55(1), 1-12.
[http://dx.doi.org/10.1002/glia.20422] [PMID: 16998865]
[60]
Murinson, B.B.; Haughey, N.J.; Maragakis, N.J. Selected statins produce rapid spinal motor neuron loss in vitro. BMC Musculoskelet. Disord., 2012, 13(1), 100.
[http://dx.doi.org/10.1186/1471-2474-13-100] [PMID: 22703530]
[61]
Kiernan, M.C.; Vucic, S.; Cheah, B.C.; Turner, M.R.; Eisen, A.; Hardiman, O.; Burrell, J.R.; Zoing, M.C. Amyotrophic lateral sclerosis. Lancet, 2011, 377(9769), 942-955.
[http://dx.doi.org/10.1016/S0140-6736(10)61156-7] [PMID: 21296405]
[62]
Golomb, B.A.; Verden, A.; Messner, A.K.; Koslik, H.J.; Hoffman, K.B. Amyotrophic lateral sclerosis associated with statin use: A disproportionality analysis of the FDA’s adverse event reporting system. Drug Saf., 2018, 41(4), 403-413.
[http://dx.doi.org/10.1007/s40264-017-0620-4] [PMID: 29427042]
[63]
Sørensen, H.T.; Riis, A.H.; Lash, T.L.; Pedersen, L. Statin use and risk of amyotrophic lateral sclerosis and other motor neuron disorders. Circ. Cardiovasc. Qual. Outcomes, 2010, 3(4), 413-417.
[http://dx.doi.org/10.1161/CIRCOUTCOMES.110.936278] [PMID: 20530788]
[64]
Freedman, D.M.; Kuncl, R.W.; Cahoon, E.K.; Rivera, D.R.; Pfeiffer, R.M. Relationship of statins and other cholesterol-lowering medications and risk of amyotrophic lateral sclerosis in the US elderly. Amyotroph. Lateral Scler. Frontotemporal Degener., 2018, 19(7-8), 538-546.
[http://dx.doi.org/10.1080/21678421.2018.1511731] [PMID: 31112080]
[65]
Yang, Z.; Wang, K.K.W. Glial fibrillary acidic protein: From intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci., 2015, 38(6), 364-374.
[http://dx.doi.org/10.1016/j.tins.2015.04.003] [PMID: 25975510]
[66]
Pfrieger, F.W. Outsourcing in the brain: Do neurons depend on cholesterol delivery by astrocytes? BioEssays, 2003, 25(1), 72-78.
[http://dx.doi.org/10.1002/bies.10195] [PMID: 12508285]
[67]
Dong, W.; Vuletic, S.; Albers, J.J. Differential effects of simvastatin and pravastatin on expression of Alzheimer’s disease-related genes in human astrocytes and neuronal cells. J. Lipid Res., 2009, 50(10), 2095-2102.
[http://dx.doi.org/10.1194/jlr.M900236-JLR200] [PMID: 19461118]
[68]
Wahrle, S.E.; Jiang, H.; Parsadanian, M.; Legleiter, J.; Han, X.; Fryer, J.D.; Kowalewski, T.; Holtzman, D.M. ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE. J. Biol. Chem., 2004, 279(39), 40987-40993.
[http://dx.doi.org/10.1074/jbc.M407963200] [PMID: 15269217]
[69]
Hirsch-Reinshagen, V.; Zhou, S.; Burgess, B.L.; Bernier, L.; McIsaac, S.A.; Chan, J.Y.; Tansley, G.H.; Cohn, J.S.; Hayden, M.R.; Wellington, C.L. Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain. J. Biol. Chem., 2004, 279(39), 41197-41207.
[http://dx.doi.org/10.1074/jbc.M407962200] [PMID: 15269218]
[70]
van Deijk, A.L.F.; Camargo, N.; Timmerman, J.; Heistek, T.; Brouwers, J.F.; Mogavero, F.; Mansvelder, H.D.; Smit, A.B.; Verheijen, M.H.G. Astrocyte lipid metabolism is critical for synapse development and function in vivo. Glia, 2017, 65(4), 670-682.
[http://dx.doi.org/10.1002/glia.23120] [PMID: 28168742]
[71]
Boehm-Cagan, A.; Bar, R.; Harats, D.; Shaish, A.; Levkovitz, H.; Bielicki, J.K.; Johansson, J.O.; Michaelson, D.M. Differential effects of apoE4 and activation of ABCA1 on brain and plasma lipoproteins. PLoS One, 2016, 11(11), e0166195.
[http://dx.doi.org/10.1371/journal.pone.0166195] [PMID: 27824936]
[72]
Rawat, V.; Wang, S.; Sima, J.; Bar, R.; Liraz, O.; Gundimeda, U.; Parekh, T.; Chan, J.; Johansson, J.O.; Tang, C.; Chui, H.C.; Harrington, M.G.; Michaelson, D.M.; Yassine, H.N. ApoE4 alters ABCA1 membrane trafficking in astrocytes. J. Neurosci., 2019, 39(48), 9611-9622.
[http://dx.doi.org/10.1523/JNEUROSCI.1400-19.2019] [PMID: 31641056]
[73]
Fields, R.D. Neuroscience. Myelin-more than insulation. Science, 2014, 344(6181), 264-266.
[http://dx.doi.org/10.1126/science.1253851] [PMID: 24744365]
[74]
Morell, P.; Jurevics, H. Origin of cholesterol in myelin. Neurochem. Res., 1996, 21(4), 463-470.
[http://dx.doi.org/10.1007/BF02527711] [PMID: 8734440]
[75]
Saher, G.; Brügger, B.; Lappe-Siefke, C.; Möbius, W.; Tozawa, R.; Wehr, M.C.; Wieland, F.; Ishibashi, S.; Nave, K.A. High cholesterol level is essential for myelin membrane growth. Nat. Neurosci., 2005, 8(4), 468-475.
[http://dx.doi.org/10.1038/nn1426] [PMID: 15793579]
[76]
Tozawa, R.; Ishibashi, S.; Osuga, J.; Yagyu, H.; Oka, T.; Chen, Z.; Ohashi, K.; Perrey, S.; Shionoiri, F.; Yahagi, N.; Harada, K.; Gotoda, T.; Yazaki, Y.; Yamada, N. Embryonic lethality and defective neural tube closure in mice lacking squalene synthase. J. Biol. Chem., 1999, 274(43), 30843-30848.
[http://dx.doi.org/10.1074/jbc.274.43.30843] [PMID: 10521476]
[77]
Klopfleisch, S.; Merkler, D.; Schmitz, M.; Klöppner, S.; Schedensack, M.; Jeserich, G.; Althaus, H.H.; Brück, W. Negative impact of statins on oligodendrocytes and myelin formation in vitro and in vivo. J. Neurosci., 2008, 28(50), 13609-13614.
[http://dx.doi.org/10.1523/JNEUROSCI.2765-08.2008] [PMID: 19074034]
[78]
Björkhem, I.; Meaney, S. Brain cholesterol: Long secret life behind a barrier. Arterioscler. Thromb. Vasc. Biol., 2004, 24(5), 806-815.
[http://dx.doi.org/10.1161/01.ATV.0000120374.59826.1b] [PMID: 14764421]
[79]
Dietschy, J.M.; Turley, S.D. Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal. J. Lipid Res., 2004, 45(8), 1375-1397.
[http://dx.doi.org/10.1194/jlr.R400004-JLR200] [PMID: 15254070]
[80]
Foran, D.R.; Peterson, A.C. Myelin acquisition in the central nervous system of the mouse revealed by an MBP-Lac Z transgene. J. Neurosci., 1992, 12(12), 4890-4897.
[http://dx.doi.org/10.1523/JNEUROSCI.12-12-04890.1992] [PMID: 1281497]
[81]
Bouslama-Oueghlani, L.; Wehrlé, R.; Sotelo, C.; Dusart, I. The developmental loss of the ability of Purkinje cells to regenerate their axons occurs in the absence of myelin: An in vitro model to prevent myelination. J. Neurosci., 2003, 23(23), 8318-8329.
[http://dx.doi.org/10.1523/JNEUROSCI.23-23-08318.2003] [PMID: 12967994]
[82]
Thompson, C.C.; Potter, G.B. Thyroid hormone action in neural development. Cereb. Cortex, 2000, 10(10), 939-945.
[http://dx.doi.org/10.1093/cercor/10.10.939] [PMID: 11007544]
[83]
McFarland, A.; Anoopkumar-Dukie, S.; Arora, D.; Grant, G.; McDermott, C.; Perkins, A.; Davey, A. Molecular mechanisms underlying the effects of statins in the central nervous system. Int. J. Mol. Sci., 2014, 15(11), 20607-20637.
[http://dx.doi.org/10.3390/ijms151120607] [PMID: 25391045]
[84]
Miron, V.E.; Rajasekharan, S.; Jarjour, A.A.; Zamvil, S.S.; Kennedy, T.E.; Antel, J.P. Simvastatin regulates oligodendroglial process dynamics and survival. Glia, 2007, 55(2), 130-143.
[http://dx.doi.org/10.1002/glia.20441] [PMID: 17078030]
[85]
Kim, S.U. Effects of the cholesterol biosynthesis inhibitor ay9944 on organotypic cultures of mouse spinal cord. Retarded myelinogenesis and induction of cytoplasmic inclusions. Lab. Invest., 1975, 32(6), 720-728.
[PMID: 50497]
[86]
Miron, V.E.; Zehntner, S.P.; Kuhlmann, T.; Ludwin, S.K.; Owens, T.; Kennedy, T.E.; Bedell, B.J.; Antel, J.P. Statin therapy inhibits remyelination in the central nervous system. Am. J. Pathol., 2009, 174(5), 1880-1890.
[http://dx.doi.org/10.2353/ajpath.2009.080947] [PMID: 19349355]
[87]
Xiang, Z.; Reeves, S.A. Simvastatin induces cell death in a mouse cerebellar slice culture (CSC) model of developmental myelination. Exp. Neurol., 2009, 215(1), 41-47.
[http://dx.doi.org/10.1016/j.expneurol.2008.09.010] [PMID: 18929563]
[88]
Smolders, I.; Smets, I.; Maier, O.; vandeVen, M.; Steels, P.; Ameloot, M. Simvastatin interferes with process outgrowth and branching of oligodendrocytes. J. Neurosci. Res., 2010, 88(15), 3361-3375.
[http://dx.doi.org/10.1002/jnr.22490] [PMID: 20857509]
[89]
Paintlia, A.S.; Paintlia, M.K.; Khan, M.; Vollmer, T.; Singh, A.K.; Singh, I. HMG-CoA reductase inhibitor augments survival and differentiation of oligodendrocyte progenitors in animal model of multiple sclerosis. FASEB J., 2005, 19(11), 1407-1421.
[http://dx.doi.org/10.1096/fj.05-3861com] [PMID: 16126908]
[90]
Sim, F.J.; Lang, J.K.; Ali, T.A.; Roy, N.S.; Vates, G.E.; Pilcher, W.H.; Goldman, S.A. Statin treatment of adult human glial progenitors induces PPARγ-mediated oligodendrocytic differentiation. Glia, 2008, 56(9), 954-962.
[http://dx.doi.org/10.1002/glia.20669] [PMID: 18383345]
[91]
Ginhoux, F.; Prinz, M. Origin of microglia: Current concepts and past controversies. Cold Spring Harb. Perspect. Biol., 2015, 7(8), a020537.
[http://dx.doi.org/10.1101/cshperspect.a020537] [PMID: 26134003]
[92]
Bi, X.; Baudry, M.; Liu, J.; Yao, Y.; Fu, L.; Brucher, F.; Lynch, G. Inhibition of geranylgeranylation mediates the effects of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors on microglia. J. Biol. Chem., 2004, 279(46), 48238-48245.
[http://dx.doi.org/10.1074/jbc.M405442200] [PMID: 15364922]
[93]
Heusinger-Ribeiro, J.; Fischer, B.; Goppelt-Struebe, M. Differential effects of simvastatin on mesangial cells. Kidney Int., 2004, 66(1), 187-195.
[http://dx.doi.org/10.1111/j.1523-1755.2004.00710.x] [PMID: 15200425]
[94]
Churchward, M.A.; Todd, K.G. Statin treatment affects cytokine release and phagocytic activity in primary cultured microglia through two separable mechanisms. Mol. Brain, 2014, 7(1), 85.
[http://dx.doi.org/10.1186/s13041-014-0085-7] [PMID: 25424483]
[95]
Zi, L.; Zhou, W.; Xu, J.; Li, J.; Li, N.; Xu, J.; You, C.; Wang, C.; Tian, M. Rosuvastatin nanomicelles target neuroinflammation and improve neurological deficit in a mouse model of intracerebral hemorrhage. Int. J. Nanomedicine, 2021, 16, 2933-2947.
[http://dx.doi.org/10.2147/IJN.S294916] [PMID: 33907400]
[96]
Carroll, J.A.; Race, B.; Phillips, K.; Striebel, J.F.; Chesebro, B. Statins are ineffective at reducing neuroinflammation or prolonging survival in scrapie-infected mice. J. Gen. Virol., 2017, 98(8), 2190-2199.
[http://dx.doi.org/10.1099/jgv.0.000876] [PMID: 28758631]
[97]
Mackenzie, I.R.A.; Munoz, D.G. Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. Neurology, 1998, 50(4), 986-990.
[http://dx.doi.org/10.1212/WNL.50.4.986] [PMID: 9566383]
[98]
Chong, P.H.; Boskovich, A.; Stevkovic, N.; Bartt, R.E. Statin-associated peripheral neuropathy: Review of the literature. Pharmacotherapy, 2004, 24(9), 1194-1203.
[http://dx.doi.org/10.1592/phco.24.13.1194.38084] [PMID: 15460180]
[99]
Casares, D.; Escribá, P.V.; Rosselló, C.A. Membrane lipid composition: Effect on membrane and organelle structure, function and compartmentalization and therapeutic avenues. Int. J. Mol. Sci., 2019, 20(9), 2167.
[http://dx.doi.org/10.3390/ijms20092167] [PMID: 31052427]
[100]
Jacobs, M.B. HMG-CoA reductase inhibitor therapy and peripheral neuropathy. Ann. Intern. Med., 1994, 120(11), 970.
[http://dx.doi.org/10.7326/0003-4819-120-11-199406010-00013] [PMID: 8172444]
[101]
Choi, H.K.; Won, E.K.; Choung, S.Y. Effect of coenzyme Q 10 supplementation in statin-treated obese rats. Biomol. Ther., 2016, 24(2), 171-177.
[http://dx.doi.org/10.4062/biomolther.2015.089] [PMID: 26797109]
[102]
Corrao, G.; Zambon, A.; Bertù, L.; Botteri, E.; Leoni, O.; Contiero, P. Lipid lowering drugs prescription and the risk of peripheral neuropathy: An exploratory case-control study using automated databases. J. Epidemiol. Community Health, 2004, 58(12), 1047-1051.
[http://dx.doi.org/10.1136/jech.2003.013409] [PMID: 15547071]
[103]
Otruba, P.; Kanovsky, P.; Hlustik, P. Treatment with statins and peripheral neuropathy: Results of 36-months a prospective clinical and neurophysiological follow-up. Neuroendocrinol. Lett., 2011, 32(5), 688-690.
[PMID: 22167150]
[104]
Tierney, E.F.; Thurman, D.J.; Beckles, G.L.; Cadwell, B.L. Association of statin use with peripheral neuropathy in the US population 40 years of age or older (Statin use and peripheral neuropathy in the US population aged 40 years and older). J. Diabetes, 2013, 5(2), 207-215.
[http://dx.doi.org/10.1111/1753-0407.12013] [PMID: 23121724]
[105]
Clark, R.S.B.; Kochanek, P.M.; Schwarz, M.A.; Schiding, J.K.; Turner, D.S.; Chen, M.; Carlos, T.M.; Watkins, S.C. Inducible nitric oxide synthase expression in cerebrovascular smooth muscle and neutrophils after traumatic brain injury in immature rats. Pediatr. Res., 1996, 39(5), 784-790.
[http://dx.doi.org/10.1203/00006450-199605000-00007] [PMID: 8726229]
[106]
Nazli, Y.; Colak, N.; Alpay, M.F.; Uysal, S.; Uzunlar, A.K.; Cakir, O. Neuroprotective effect of atorvastatin in spinal cord ischemia-reperfusion injury. Clinics, 2015, 70(1), 52-60.
[http://dx.doi.org/10.6061/clinics/2015(01)10] [PMID: 25672430]
[107]
Fisher, M.; Moonis, M. Neuroprotective effects of statins: Evidence from preclinical and clinical studies. Curr. Treat. Options Cardiovasc. Med., 2012, 14(3), 252-259.
[http://dx.doi.org/10.1007/s11936-012-0174-9] [PMID: 22362392]
[108]
Kosowski, M.; Smolarczyk-Kosowska, J.; Hachuła, M.; Maligłówka, M.; Basiak, M.; Machnik, G.; Pudlo, R.; Okopień, B. The effects of statins on neurotransmission and their neuroprotective role in neurological and psychiatric disorders. Molecules, 2021, 26(10), 2838.
[http://dx.doi.org/10.3390/molecules26102838] [PMID: 34064670]
[109]
Endoh, M.; Maiese, K.; Wagner, J. Expression of the inducible form of nitric oxide synthase by reactive astrocytes after transient global ischemia. Brain Res., 1994, 651(1-2), 92-100.
[http://dx.doi.org/10.1016/0006-8993(94)90683-1] [PMID: 7522935]
[110]
Hu, S.; Sheng, W.S.; Peterson, P.K.; Chao, C.C. Differential regulation by cytokines of human astrocyte nitric oxide production. Glia, 1995, 15(4), 491-494.
[http://dx.doi.org/10.1002/glia.440150412] [PMID: 8926042]
[111]
Cespuglio, R.; Amrouni, D.; Raymond, E.F.; Bouteille, B.; Buguet, A. Cerebral inducible nitric oxide synthase protein expression in microglia, astrocytes and neurons in Trypanosoma brucei brucei-infected rats. PLoS One, 2019, 14(4), e0215070.
[http://dx.doi.org/10.1371/journal.pone.0215070] [PMID: 30995270]
[112]
Pahan, K.; Sheikh, F.G.; Namboodiri, A.M.; Singh, I. Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. J. Clin. Invest., 1997, 100(11), 2671-2679.
[http://dx.doi.org/10.1172/JCI119812] [PMID: 9389730]
[113]
Vaughan, C.J.; Delanty, N. Neuroprotective properties of statins in cerebral ischemia and stroke. Stroke, 1999, 30(9), 1969-1973.
[http://dx.doi.org/10.1161/01.STR.30.9.1969] [PMID: 10471452]
[114]
Ghayour, M.B.; Abdolmaleki, A.; Rassouli, M.B. Neuroprotective effect of Lovastatin on motor deficit induced by sciatic nerve crush in the rat. Eur. J. Pharmacol., 2017, 812, 121-127.
[http://dx.doi.org/10.1016/j.ejphar.2017.07.018] [PMID: 28688913]
[115]
Bösel, J.; Gandor, F.; Harms, C.; Synowitz, M.; Harms, U.; Djoufack, P.C.; Megow, D.; Dirnagl, U.; Hörtnagl, H.; Fink, K.B.; Endres, M. Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. J. Neurochem., 2005, 92(6), 1386-1398.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02980.x] [PMID: 15748157]
[116]
Gao, K.; Wang, G.; Wang, Y.; Han, D.; Bi, J.; Yuan, Y.; Yao, T.; Wan, Z.; Li, H.; Mei, X. Neuroprotective effect of simvastatin via inducing the autophagy on spinal cord injury in the rat model. BioMed Res. Int., 2015, 2015, 1-9.
[http://dx.doi.org/10.1155/2015/260161] [PMID: 26539474]

Rights & Permissions Print Cite
Article Metrics
40
2
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy