Alzheimer’s disease: pathological mechanisms and the beneficial role of melatonin

Journal of Pineal Research - Tập 52 Số 2 - Trang 167-202 - 2012
Sergio Rosales‐Corral1,2, Darío Acuña‐Castroviejo3, Ana Coto‐Montes2, José Antonio Boga2, Lucien C. Manchester2, Lorena Fuentes‐Broto2, Ahmet Korkmaz2, Shuran Ma2, Dun Xian Tan2, Rüssel J. Reiter2
1Centro de Investigación Biomédica de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México
2Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
3Departamento de Fisiología, Instituto de Biotecnología, Universidad de Granada, Granada, Spain

Tóm tắt

Abstract:  Alzheimer’s disease (AD) is a highly complex neurodegenerative disorder of the aged that has multiple factors which contribute to its etiology in terms of initiation and progression. This review summarizes these diverse aspects of this form of dementia. Several hypotheses, often with overlapping features, have been formulated to explain this debilitating condition. Perhaps the best‐known hypothesis to explain AD is that which involves the role of the accumulation of amyloid‐β peptide in the brain. Other theories that have been invoked to explain AD and summarized in this review include the cholinergic hypothesis, the role of neuroinflammation, the calcium hypothesis, the insulin resistance hypothesis, and the association of AD with peroxidation of brain lipids. In addition to summarizing each of the theories that have been used to explain the structural neural changes and the pathophysiology of AD, the potential role of melatonin in influencing each of the theoretical processes involved is discussed. Melatonin is an endogenously produced and multifunctioning molecule that could theoretically intervene at any of a number of sites to abate the changes associated with the development of AD. Production of this indoleamine diminishes with increasing age, coincident with the onset of AD. In addition to its potent antioxidant and anti‐inflammatory activities, melatonin has a multitude of other functions that could assist in explaining each of the hypotheses summarized above. The intent of this review is to stimulate interest in melatonin as a potentially useful agent in attenuating and/or delaying AD.

Từ khóa


Tài liệu tham khảo

10.1056/NEJMra0909142

Alzheimer’s Association, 2011, 2011 Alzheimer’s disease facts and figures, Alzheimers Dement, 7, 208, 10.1016/j.jalz.2011.02.004

10.1001/archneur.60.8.1119

10.1111/j.1755-5949.2010.00175.x

10.2165/00002512-200724020-00007

10.1212/01.wnl.0000265223.25679.2a

10.1212/WNL.0b013e3181a18691

10.1212/WNL.54.3.588

10.1212/WNL.62.1.66

10.1002/msj.20165

Jansen SL, 2006, Melatonin for cognitive impairment, Cochrane Database Syst Rev, 25, CD003802

10.1007/s12640-009-9121-2

Cardinali DP, 2002, The use of melatonin in Alzheimer’s disease, Neuro Endocrinol Lett, 23, 20

10.1523/JNEUROSCI.17-05-01683.1997

Wang XC, 2005, Prevention of isoproterenol‐induced tau hyperphosphorylation by melatonin in the rat, Sheng Li Xue Bao, 57, 7

Van Rensburg SJ, 1997, A new model for the pathophysiology of Alzheimer’s disease. Aluminium toxicity is exacerbated by hydrogen peroxide and attenuated by an amyloid protein fragment and melatonin, S Afr Med J, 87, 1111

10.1177/0269881110367723

10.1093/sleep/26.7.893

10.1002/jnr.22201

10.1111/j.1600-079X.2009.00692.x

10.1016/j.tox.2009.09.009

10.1034/j.1600-079X.2003.00065.x

10.1210/jc.84.1.323

10.1016/j.neurobiolaging.2005.12.004

10.3233/JAD-2009-0949

10.1210/edrv-12-2-151

Greilberger J, 2010, Carbonyl proteins as a clinical marker in Alzheimer’s disease and its relation to tryptophan degradation and immune activation, Clin Lab, 56, 441

10.1001/archneur.1991.00530180075020

10.1056/NEJMoa011613

10.2967/jnumed.109.063008

10.1023/A:1003431122334

Kvetnoy IM, 2000, Letter to the Editor. Claude Bernard was right: hormones may be produced by ‘non‐endocrine’ cells, Neuro Endocrinol Lett, 21, 173

10.1159/000014640

10.1111/j.1600-079X.2010.00773.x

10.1111/j.1749-6632.2001.tb03627.x

10.1111/j.1600-079X.2009.00721.x

10.1111/j.1600-079X.2010.00778.x

10.1111/j.1600-079X.2010.00779.x

10.2174/157015910792246236

10.1385/ENDO:27:2:189

10.1111/j.1600-079X.2010.00748.x

10.1111/j.1600-079X.2010.00752.x

10.1080/15622970600571822

10.1586/ern.10.1

10.1111/j.1600-079X.2010.00754.x

10.1177/1534735409353332

10.1111/j.1600-079X.2010.00794.x

10.1007/BF01923947

10.1095/biolreprod.108.075655

10.1126/science.7434032

10.1210/endo-109-4-1295

10.1111/j.1600-079X.1986.tb00760.x

10.1002/bies.950140307

10.1111/j.1600-079X.2004.00196.x

10.1126/science.1167425

TanDX ChenLD PoeggelerBet al.Melatonin: a potent endogenous hydroxyl radical scavenger.1993;1:57–60.

10.1039/c0cp02801k

10.1111/j.1600-079X.1993.tb00498.x

10.1080/10409230903044914

10.18388/abp.2007_3264

10.1111/j.1600-079X.1998.tb00387.x

10.1034/j.1600-079X.2001.280201.x

10.1016/j.ejmech.2008.12.017

10.1016/j.lfs.2006.09.011

10.1016/S0891-5849(00)00435-4

10.1016/j.mrgentox.2003.12.009

10.1562/0031-8655(2003)0780449IOSMOW2.0.CO2

10.1074/jbc.M506384200

10.1007/BF03345555

10.1385/CBB:34:2:237

10.2174/1568026023394443

10.1016/S0891-5849(96)00614-4

10.1111/j.1600-079X.2006.00407.x

10.1111/j.1600-079X.2010.00771.x

10.1111/j.1600-079X.2009.00723.x

10.1096/fj.01-0309fje

10.1016/S0021-9258(19)42976-1

10.1111/j.1600-079X.2009.00701.x

10.1179/135100003225002709

10.1016/j.nbd.2007.07.018

10.1021/bi051525c

10.1021/jm980123i

10.2174/1568026023394335

10.1016/0197-0186(94)00154-M

10.1111/j.1600-079X.1995.tb00178.x

10.1046/j.1600-079X.2003.00092.x

Kilanczyk E, 2003, The effect of melatonin on antioxidant enzymes in human diabetic skin fibroblasts, Cell Mol Biol Lett, 8, 333

10.1034/j.1600-079X.2001.300103.x

10.1007/s00221-005-2338-2

10.1111/j.1600-079X.1998.tb00380.x

10.1016/j.freeradbiomed.2005.08.014

10.1002/hipo.20612

10.1096/fasebj.2.12.2842214

10.1042/BJ20071373

10.1096/fasebj.12.12.1211

10.1016/j.pneurobio.2010.12.004

10.1016/S0079-6123(08)81008-4

10.1056/NEJMra040223

10.1016/j.biocel.2009.03.015

10.1016/S0197-4580(02)00050-7

10.1523/JNEUROSCI.23-13-05531.2003

10.1097/00001756-199704140-00039

10.1523/JNEUROSCI.1450-06.2006

10.1074/jbc.M110.137729

10.1023/A:1022809003997

10.1016/S0301-0082(03)00089-3

10.1042/bj2470085

10.1073/pnas.96.7.3922

10.1016/S0021-9258(18)53650-4

10.1016/S0006-291X(02)00302-9

10.1074/jbc.273.43.27765

10.2174/092986707782360060

10.2174/156720508783954668

10.1007/BF03402076

10.2174/156720508783954758

10.1016/j.nbd.2007.10.005

10.1083/jcb.200207113

10.1073/pnas.241509198

10.1038/19077

10.1038/34910

10.1159/000095267

10.1016/j.bbalip.2010.03.008

10.1126/science.1074069

10.1016/j.nbd.2005.02.008

10.1038/nn1503

10.1016/S0896-6273(03)00124-7

10.1016/S0306-4522(02)00132-X

10.1073/pnas.89.16.7437

Bayer TA, 2010, Intracellular accumulation of amyloid‐Beta – a predictor for synaptic dysfunction and neuron loss in Alzheimer’s disease, Front Aging Neurosci, 2, 1

10.1016/S0002-9440(10)64700-1

10.1111/j.1742-4658.2010.07568.x

10.1042/0264-6021:3480307

10.1074/jbc.M407101200

10.1016/S0960-9822(01)00394-3

10.1073/pnas.0230450100

10.1074/jbc.273.49.32730

10.1523/JNEUROSCI.21-08-02561.2001

10.1096/fasebj.14.7.1015

10.1038/nature01640

10.1186/1750-1326-5-46

10.1074/jbc.R800016200

10.1007/s11064-004-7035-1

10.1038/416535a

10.1073/pnas.95.11.6448

10.1523/JNEUROSCI.3432-04.2004

10.1126/science.290.5495.1364

10.1080/10715760802277388

10.1074/jbc.273.13.7185

10.1021/bi0114269

10.1016/S0006-3495(91)82154-3

10.1016/S0166-1280(03)00100-3

10.1002/jms.243

10.1046/j.1471-4159.2003.01654.x

10.1007/BF02736852

10.1111/j.1600-079X.1999.tb00575.x

Lee RK, 1999, Prostaglandin E2 stimulates amyloid precursor protein gene expression: inhibition by immunosuppressants, J Neurosci, 19, 940, 10.1523/JNEUROSCI.19-03-00940.1999

10.1016/j.jneuroim.2005.05.002

10.1002/ana.10072

10.1210/endo.138.2.4925

10.1006/bbrc.2001.5273

10.4196/kjpp.2008.12.2.37

10.1016/j.bbamcr.2008.02.016

10.1016/j.neulet.2004.08.068

10.1089/ars.2009.2629

Biessels GJ, 2005, Increased risk of Alzheimer’s disease in Type II diabetes: insulin resistance of the brain or insulin‐induced amyloid pathology?, Biochem Soc Trans, 33, 1041, 10.1042/BST0331041

10.1111/j.1600-079X.2010.00747.x

10.1074/jbc.M608856200

10.1016/S0014-5793(03)00807-X

10.3233/JAD-2006-9105

10.1016/S0896-6273(03)00367-2

10.1116/1.2804746

10.1016/j.jsb.2009.06.020

10.1111/j.1600-079X.2004.00121.x

10.1111/j.1600-079X.2004.00144.x

10.1126/science.274.5284.99

10.1016/j.brainres.2005.01.023

10.1042/BST0370692

10.1016/S0197-4580(01)00342-6

10.1016/j.mehy.2007.02.034

10.1001/archneur.55.11.1449

10.1167/iovs.09-3402

10.1016/j.neuroscience.2005.05.048

10.1126/science.7046051

10.1136/jnnp.66.2.137

10.1016/j.neuropharm.2010.06.005

Guermonprez L, 2001, Inhibition of acetylcholine synthesis and tyrosine nitration induced by peroxynitrite are differentially prevented by antioxidants, Mol Pharmacol, 60, 838

10.1073/pnas.93.15.8068

10.1196/annals.1306.004

Schweitzer ES, 1993, Regulated and constitutive secretion of distinct molecular forms of acetylcholinesterase from PC12 cells, J Cell Sci, 106, 731, 10.1242/jcs.106.3.731

10.1046/j.1471-4159.1997.69031177.x

10.1016/S0168-0102(02)00201-8

10.1016/j.ejphar.2010.04.041

10.1097/00001756-199511270-00031

10.1006/exnr.1997.6599

10.1016/j.biocel.2006.06.012

Zhang QZ, 1999, Inhibitory effects of melatonin on free intracellular calcium in mouse brain cells, Zhongguo Yao Li Xue Bao, 20, 206

10.1111/j.1600-079X.2008.00554.x

10.1016/j.bbr.2008.01.015

10.1523/JNEUROSCI.17-08-02653.1997

10.1001/jama.281.15.1433

10.1124/mol.107.040881

10.1111/j.1745-7254.2006.00260.x

10.1016/S0891-5849(02)00794-3

10.1074/jbc.274.4.2234

10.1016/S0024-3205(02)02105-7

10.1126/science.1566067

10.2174/138161206778343109

10.1177/011542650802300135

10.1089/ars.2008.2256

10.1111/j.1471-4159.1986.tb00615.x

10.1016/j.freeradbiomed.2010.02.016

10.1111/j.1582-4934.2008.00478.x

10.1038/382674a0

10.1016/j.jneuroim.2004.01.005

10.1523/JNEUROSCI.18-06-02161.1998

10.1038/382685a0

10.1186/1756-6606-2-31

10.1159/000088929

10.1111/j.1471-4159.2008.05347.x

10.1021/bi026173d

10.1186/1742-2094-3-24

10.1006/bbrc.2000.2897

10.1152/physrev.00029.2006

10.1089/ars.2009.2578

Harraz MM, 2008, SOD1 mutations disrupt redox‐sensitive Rac regulation of NADPH oxidase in a familial ALS model, J Clin Invest, 118, 659

10.1371/journal.pone.0000536

10.1096/fj.04-2582fje

10.1073/pnas.0903563106

10.1016/j.bbagen.2009.08.003

10.1021/bi000169p

10.1016/j.bbapap.2004.10.014

10.1021/tx0101550

10.1016/j.freeradbiomed.2007.05.037

10.1021/bi990438f

10.1111/j.1460-9568.2009.06701.x

10.1016/S0022-510X(96)00203-1

10.1016/S0022-510X(98)00092-6

10.1016/S0169-328X(00)00049-8

10.1111/j.1749-6632.2002.tb02096.x

Milton NG, 1999, Amyloid‐beta binds catalase with high affinity inhibits hydrogen peroxide breakdown, Biochem J, 344, 293, 10.1042/bj3440293

10.1073/pnas.0902714106

10.1038/nm0198-097

10.1016/j.freeradbiomed.2008.03.012

10.1016/S0896-6273(03)00434-3

10.1093/qjmed/92.1.39

10.1186/1742-2094-1-14

10.1016/S0197-4580(00)00124-X

10.1172/JCI31450

10.1189/jlb.0306164

10.1186/1742-2094-5-43

10.1016/S0014-5793(01)02437-1

10.1016/j.freeradbiomed.2004.10.016

10.1083/jcb.200705042

10.4049/jimmunol.181.10.7254

10.1093/brain/awl249

10.1016/j.bbrc.2008.04.148

10.1074/jbc.M208788200

10.1111/j.1471-4159.2010.06637.x

10.2217/14796708.4.2.167

10.1016/j.neurobiolaging.2008.05.017

10.1046/j.1471-4159.2000.0740143.x

10.1523/JNEUROSCI.23-07-02665.2003

10.1016/j.bbagrm.2010.05.004

10.1073/pnas.92.20.9328

10.1016/0098-2997(93)90004-W

10.1074/jbc.274.22.15493

10.1152/jn.00696.2004

10.1007/s11064-008-9612-1

10.1007/s00424-010-0809-1

10.1111/j.1600-079X.2008.00570.x

10.1089/ars.2006.8.1749

10.1016/j.freeradbiomed.2005.03.007

10.1111/j.1471-4159.2006.04029.x

10.1006/exnr.1997.6738

10.1016/j.nbd.2006.01.004

10.1016/j.biocel.2004.10.004

10.1042/AN20090035

10.1038/ni.1636

10.1096/fj.01-0514fje

10.1002/cne.20779

10.1016/j.brainres.2004.09.064

10.1111/j.1600-079X.2008.00582.x

Kim YS, 2007, The effect of melatonin on glutamate‐ and its subtype agonists‐ induced ion currents in rat hippocampal CA1 neurons, FASEB J, 21, A1277

Zhang QZ, 1999, Antagonistic effects of melatonin on glutamate release and neurotoxicity in cerebral cortex, Zhongguo Yao Li Xue Bao, 20, 829

10.1034/j.1600-079X.2003.00057.x

Natarajan M, 1995, The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF‐kappa B, Biochem Mol Biol Int, 37, 1063

10.1006/cbir.1996.0091

10.1016/S0009-2797(00)00319-7

10.1016/j.arcmed.2006.10.007

10.1074/jbc.M605741200

10.1006/exnr.1996.0043

10.1172/JCI11916

10.1182/blood-2005-09-3691

10.1186/1471-230X-2-9

10.1096/fj.03-0323fje

10.1002/hipo.20650

10.1007/BF00611091

10.1002/hipo.1105

10.1016/j.neulet.2005.09.040

10.1002/jnr.10605

10.1002/glia.10109

10.1074/jbc.270.13.7037

10.1016/S0021-9258(19)61934-4

10.1093/nar/23.3.327

10.1016/j.neurobiolaging.2006.06.007

10.1096/fj.07-9131.com

10.1016/S0165-5728(01)00419-2

Negi G, 2010, Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: effects on NF‐kappaB and Nrf2 cascades, J Pineal Res, 50, 124, 10.1111/j.1600-079X.2010.00821.x

10.1034/j.1600-079X.2003.00010.x

10.1016/S1474-4422(04)00707-0

10.1016/j.expneurol.2009.01.011

10.1016/0304-3940(80)90220-7

10.1002/ana.410170505

10.1212/WNL.40.8.1302

10.1126/science.1072994

10.1016/0165-6147(91)90609-V

10.1096/fj.05-3735fje

10.1016/j.freeradbiomed.2009.02.028

10.1016/j.febslet.2005.04.041

10.1179/016164103101201977

10.1002/jnr.10648

10.1126/science.1091230

10.1096/fj.01-0377com

10.1046/j.1471-4159.2001.00112.x

10.1016/S0014-5793(99)01028-5

10.1073/pnas.0806192105

10.2165/11532140-000000000-00000

10.1523/JNEUROSCI.1357-09.2009

10.1126/science.1171091

10.1385/NMM:2:2:215

10.1007/s10863-009-9239-1

10.1126/science.1112125

10.1016/j.mehy.2003.12.045

10.1006/bbrc.2001.4370

10.2174/156720508785908946

10.1038/nm.1868

10.1042/bj3020321

10.1016/S0005-2728(98)00119-4

Martinez‐Cano E, 2005, [Functional disorders of FOF1‐ATPase in submitochondrial particles obtained from platelets of patients with a diagnosis of probable Alzheimer’s disease], Rev Neurol, 40, 81

10.1523/JNEUROSCI.15-09-06239.1995

10.1016/S0197-4580(01)00314-1

10.1111/j.1600-079X.2004.00140.x

10.1016/j.lfs.2004.03.003

10.1111/j.1600-079X.2007.00490.x

10.2174/156802611794863517

10.1096/fj.99-0865fje

10.1097/00005072-199712000-00010

10.1111/j.1600-079X.2009.00700.x

10.1371/journal.pone.0010206

10.1096/fj.03-1031fje

10.1038/nchembio0905-188

10.1016/j.freeradbiomed.2009.06.032

10.1111/j.1600-079X.2010.00759.x

10.2353/ajpath.2008.080434

Ling X, 1999, Protective effect of melatonin on injured cerebral neurons is associated with bcl‐2 protein over‐expression, Zhongguo Yao Li Xue Bao, 20, 409

10.1523/JNEUROSCI.16-23-07533.1996

10.1016/j.neulet.2005.01.003

10.1016/0197-4580(95)02024-1

10.1111/j.1600-079X.2004.00166.x

10.1111/j.1600-079X.2009.00680.x

10.1111/j.1600-079X.2004.00164.x

10.2741/A251

10.1016/0006-8993(94)91505-9

10.1523/JNEUROSCI.12-02-00376.1992

10.1016/S0306-4522(97)00053-5

10.3233/JAD-2001-3507

10.1007/978-1-4020-6191-2_19

10.1074/jbc.M602061200

10.1021/bi00181a016

10.1002/gps.938

10.1016/0303-7207(94)03437-X

10.1016/S0197-0186(99)00120-5

Brunner P, 2006, Pineal and cortical melatonin receptors MT1 and MT2 are decreased in Alzheimer’s disease, Eur J Histochem, 50, 311

10.1016/0006-8993(88)90404-0

10.1016/S0304-3940(01)02188-7

10.1046/j.1365-2826.2001.00656.x

10.1111/j.1365-2826.2004.01250.x

10.1007/s11010-006-2385-4

10.1002/(SICI)1097-4644(19970601)65:3<430::AID-JCB12>3.0.CO;2-J

10.1002/neu.480160308

10.1007/BF01923944

10.1111/j.1600-079X.1996.tb00260.x

Turjanski AG, 2007, Melatonin – From Molecules to Therapy, 47

10.1016/0304-4165(96)00025-6

10.1111/j.1600-079X.1994.tb00114.x

10.1016/S0014-4886(03)00085-2

10.1016/S0197-0186(01)00021-3

10.2174/157015908785777201

Benitez‐KingG Ortiz‐LopezL Jimenez‐RubioG.Melatonin precludes cytoskeletal collapse caused by hydrogen peroxide: participation of protein kinase C.2005;2:767–778.

10.1046/j.1432-1033.2003.03430.x

10.1016/S0197-4580(00)00247-5

10.1111/j.1600-079X.2008.00656.x

10.1523/JNEUROSCI.22-09-03359.2002

10.1001/archneur.65.10.1368

10.1159/000067423

10.1091/mbc.e08-07-0777

10.1007/s007020050068

10.1016/j.bcp.2008.12.006

10.1016/0014-5793(94)00387-4

10.1186/1476-511X-5-28

10.1586/14737175.4.1.79

Niikura T, 2001, Insulin‐like growth factor I (IGF‐I) protects cells from apoptosis by Alzheimer’s V642I mutant amyloid precursor protein through IGF‐I receptor in an IGF‐binding protein‐sensitive manner, J Neurosci, 21, 1902, 10.1523/JNEUROSCI.21-06-01902.2001

10.1073/pnas.94.9.4772

10.2337/diabetes.53.2.474

10.1093/aje/154.7.635

10.1096/fj.03-0978fje

10.1523/JNEUROSCI.22-10-j0001.2002

10.1002/j.1460-2075.1986.tb04528.x

10.1074/jbc.M000238200

10.1210/endo-122-6-2558

10.1111/j.1600-079X.1995.tb00164.x

Jale O, 2009, Melatonin Increases the Expression of Insulin‐like Growth Factor I in Rats with Carbontetrachlorid‐Induced Hepatic Damage, Anim Vet Adv, 8, 2251

10.1002/glia.20940

Pawlikowski M, 2002, Effects of six months melatonin treatment on sleep quality and serum concentrations of estradiol, cortisol, dehydroepiandrosterone sulfate, and somatomedin C in elderly women, Neuro Endocrinol Lett, 23, 17

10.1016/S0140-6736(95)91382-3

10.1210/jc.2001-011441

10.1034/j.1600-079x.2002.00841.x

10.1111/j.1471-4159.2004.02514.x

10.1074/jbc.M008552200

10.1016/S0092-8674(00)80405-5

10.1172/JCI115796

10.1073/pnas.170008497

10.1016/j.nbd.2008.08.002

10.1016/j.mehy.2006.11.012

10.1016/S0167-4889(00)00127-0

10.1111/j.1600-079X.2007.00496.x

10.1371/journal.pone.0007128

10.1111/j.1600-079X.2007.00519.x

10.1111/j.1600-079X.2010.00804.x

10.1111/j.1600-079X.2006.00386.x

10.1111/j.1600-079X.2010.00826.x

10.1016/j.cbpa.2009.12.006

10.1016/0197-4580(94)90152-X

10.1210/en.2009-0425

10.1111/j.1600-079X.2006.00334.x

10.1016/S0022-2275(20)32101-5

10.1111/j.1471-4159.2007.04715.x

10.1038/ncb1313

10.1073/pnas.032395699

10.1111/j.1600-0404.2006.00682.x

10.1074/jbc.M210047200

10.1073/pnas.95.11.6460

10.1073/pnas.081620098

10.1046/j.1471-4159.1997.69041746.x

10.1083/jcb.200404149

10.1136/bmj.322.7300.1447

10.1016/j.neulet.2010.06.080

10.2174/156720508783884675

10.1186/1750-1326-4-47

10.1186/1742-2094-3-28

10.1007/BF02536067

10.1079/BJN2002804

10.1177/070674370304800308

10.1023/A:1027341707837

10.1016/j.neulet.2007.04.086

10.1016/S0306-4522(99)00107-4

10.1046/j.1440-1681.2001.03437.x

10.1093/jn/138.6.1165

10.1016/j.neuroscience.2006.01.021

10.1016/j.neuroscience.2009.02.057

10.1523/JNEUROSCI.1071-09.2009

10.1016/S0024-3205(97)00030-1

10.3109/07853890.2011.586365

Rosales‐CorralS OrtizG Valdivia‐VelazquezM.Oxidative stress in rat brain induced by amyloid‐beta under continuous light conditions.2004;154:170–170.

10.1039/b715278g

10.1016/S0002-9440(10)63724-8

10.1002/ana.22234

10.1046/j.1471-4159.1997.69052220.x

10.1096/fasebj.14.10.1464

10.1016/j.taap.2009.05.011

10.1042/bj3510709

10.1111/j.1600-079X.2006.00415.x

10.1016/S0006-291X(02)00336-4

10.1034/j.1600-079X.2001.280302.x

10.1111/j.1600-079X.2005.00211.x

10.1523/JNEUROSCI.0862-09.2009

10.1016/j.mehy.2009.12.026

10.1016/j.neurobiolaging.2006.06.002

10.1016/0531-5565(93)90074-N

Trapp GA, 1978, Aluminum levels in brain in Alzheimer’s disease, Biol Psychiatry, 13, 709

10.1016/S0197-4580(02)00133-1

10.1016/S0924-977X(98)00022-4

10.1111/j.1749-6632.1986.tb51265.x

10.1016/j.yebeh.2004.01.012

Cohen DA, 2010, Ramelteon prior to a short evening nap impairs neurobehavioral performance for up to 12 hours after awakening, J Clin Sleep Med, 6, 565, 10.5664/jcsm.27990

Dhand R, 2006, Good sleep, bad sleep! The role of daytime naps in healthy adults, Curr Opin Pulm Med, 12, 379

10.1001/jama.1972.03200140072031

10.1038/214919a0

Hardeland R, 2008, Melatonergic drugs in clinical practice, Arzneimittelforschung, 58, 1