Melatonin and Abeta, Macular Degeneration and Alzheimers Disease: Same Disease, Different Outcomes?
Medical hypothesis discovery and innovation in ophthalmology,
Vol. 1 No. 2 (2012),
1 June 2012
,
Page 24-32
Abstract
Aging is the common denominator and the highest risk factor for macular degeneration and Alzheimers Disease (AD). Important pathological hallmarks common to both diseases are the presence of amyloid β (Aβ) in the senile plaques of the AD brain and in the drusen of age-related macular degeneration (AMD) patients, oxidative stress, and apoptotic cell death. Data suggest that a common pathogenic mechanism might exist between AMD and AD. Brain and eye depend on redox electrons from pyridinic and flavinic nucleotides to produce ATP, and reactive oxygen intermediates (ROI). Disorganization of mitochondrial structure and decline in mitochondrial oxidative phosphorylation (OXPHOS) functioning, as well as hypometabolism and alterations in mitochondrial DNA are aging features. Because ROI damage and mitochondrial dysregulation are prominent in AMD and AD and their relationship to the redox state is unclear we addressed a new hypothesis according to which the interaction of melatonin vs Aβ are intertwined to balance of the intra- and extra-mitochondrial energy production. This balance would be impaired by the ageing process and environmental/genetic factors, ultimately leading to AD and /or AMD.
References
Gehrs KM, Anderson DH, Johnson LV, Hageman GS. Age-related macular degeneration--emerging pathogenetic and therapeutic concepts. Ann Med.2006;38(7):450-71. PMID: 17101537.
Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003 Aug;60(8):1119-22. PMID: 12925369.
Ohno-Matsui K. Parallel findings in age-related macular degeneration and Alzheimer's disease. Prog Retin Eye Res. 2011 Jul;30(4):217-38. PMID: 21440663.
Klaver CC, Ott A, Hofman A, Assink JJ, Breteler MM, de Jong PT. Is age-related maculopathy associated with Alzheimer's Disease? The Rotterdam Study. Am J Epidemiol. 1999 Nov 1;150(9):963-8. PMID: 10547142.
Rudnicka AR, Jarrar Z, Wormald R, Cook DG, Fletcher A, Owen CG. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis. Ophthalmology. 2012 Mar;119(3):571-80. PMID: 22176800.
Bajić VP, Spremo-Potparević B, Zivković L, Bonda DJ, Siedlak SL, Casadesus G, Lee HG, Smith MA. The X-chromosome instability phenotype in Alzheimer's disease: a clinical sign of accelerating aging? Med Hypotheses. 2009 Dec;73(6):917-20. PMID: 19647374.
Damoiseaux JS, Seeley WW, Zhou J, Shirer WR, Coppola G, Karydas A, Rosen HJ, Miller BL, Kramer JH, Greicius MD; Alzheimer's Disease Neuroimaging Initiative. Gender modulates the APOE ε4 effect in healthy older adults: convergent evidence from functional brain connectivity and spinal fluid tau levels. J Neurosci. 2012 Jun 13;32(24):8254-62. PMID: 22699906.
Dowling JE. The Retina: An Approachable Part of the Brain. Cambridge, MA: Harvard University Press; 1987. p. 1-282.
Tuppo EE, Arias HR. The role of inflammation in Alzheimer's disease. Int J Biochem Cell Biol. 2005 Feb;37(2):289-305. PMID: 15474976.
Ho T, Vessey KA, Cappai R, Dinet V, Mascarelli F, Ciccotosto GD, Fletcher EL. Amyloid precursor protein is required for normal function of the rod and cone pathways in the mouse retina. PLoS One. 2012;7(1):e29892. PMID: 22279552.
Dowling JK, O'Neill LA. Biochemical regulation of the inflammasome. Crit Rev Biochem Mol Biol. 2012 Jun 11. [Epub ahead of print]
Salminen A, Ojala J, Kaarniranta K, Kauppinen A.Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases.Cell Mol Life Sci. 2012 Mar 25 [Epub ahead of print]
Lee SH, Kim KR, Ryu SY, Son S, Hong HS, Mook-Jung I, Lee SH, Ho WK. Impaired short-term plasticity in mossy fiber synapses caused by mitochondrial dysfunction of dentate granule cells is the earliest synaptic deficit in a mouse model of Alzheimer's disease. J Neurosci. 2012 Apr 25;32(17):5953-63. PMID: 22539855.
Ho GJ, Drego R, Hakimian E, Masliah E. Mechanisms of cell signaling and inflammation in Alzheimer's disease. Curr Drug Targets Inflamm Allergy. 2005 Apr;4(2):247-56. PMID: 15853747.
Kann O, Kovács R. Mitochondria and neuronal activity. Am J Physiol Cell Physiol. 2007 Feb;292(2):C641-57. PMID: 17092996.
Ames A 3rd. CNS energy metabolism as related to function. Brain Res Brain Res Rev. 2000 Nov;34(1-2):42-68.PMID: 11086186.
Zeviani M, Di Donato S. Mitochondrial disorders. Brain. 2004 Oct;127(Pt 10):2153-72. Erratum in: Brain. 2004 Dec;127(Pt 12):2783. PMID: 15358637.
Bratic I, Trifunovic A. Mitochondrial energy metabolism and ageing. Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):961-7. PMID: 20064485.
Zeth K, Thein M. Porins in prokaryotes and eukaryotes: common themes and variations. Biochem J. 2010 Oct 1;431(1):13-22. PMID: 20836765.
Panfoli I, Calzia D, Ravera S, Bruschi M, Tacchetti C, Candiani S, Morelli A, Candiano G. Extramitochondrial tricarboxylic acid cycle in retinal rod outer segments. Biochimie. 2011 Sep;93(9):1565-75. PMID: 21683117.
Habersetzer J, Ziani W, Larrieu I, Stines-Chaumeil C, Giraud MF, Brèthes D, Dautant A, Paumard P. ATP synthase oligomerization: from the enzyme models to the mitochondrial morphology. Int J Biochem Cell Biol. 2013 Jan;45(1):99-105. PMID: 22664329.
Panfoli I, Calzia D, Bianchini P, Ravera S, Diaspro A, Candiano G, Bachi A, Monticone M, Aluigi MG, Barabino S, Calabria G, Rolando M, Tacchetti C, Morelli A, Pepe IM. Evidence for aerobic metabolism in retinal rod outer segment disks.Int J Biochem Cell Biol. 2009 Dec;41(12):2555-65. PMID: 19715769.
Ravera S, Panfoli I, Calzia D, Aluigi MG, Bianchini P, Diaspro A, Mancardi G, Morelli A. Evidence for aerobic ATP synthesis in isolated myelin vesicles. Int J Biochem Cell Biol. 2009 Jul;41(7):1581-91. PMID: 19401152.
Adriano E, Perasso L, Panfoli I, Ravera S, Gandolfo C, Mancardi G, Morelli A, Balestrino M. A novel hypothesis about mechanisms affecting conduction velocity of central myelinated fibers. Neurochem Res. 2011 Oct;36(10):1732-9. PMID: 21553257.
Panfoli I, Ravera S, Bruschi M, Candiano G, Morelli A. Proteomics unravels the exportability of mitochondrial respiratory chains. Expert Rev Proteomics. 2011 Apr;8(2):231-9. PMID: 21501016.
Gregersen N, Hansen J, Palmfeldt J. Mitochondrial proteomics-a tool for the study of metabolic disorders. J Inherit Metab Dis. 2012 (in press)
McBride HM, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse. Curr Biol. 2006 Jul 25;16(14):R551-60. PMID: 16860735.
Bianchini P, Calzia D, Ravera S, Candiano G, Bachi A, Morelli A, Bruschi M, Pepe IM, Diaspro A, Panfoli I. Live imaging of mammalian retina: rod outer segments are stained by conventional mitochondrial dyes. J Biomed Opt. 2008 Sep-Oct;13(5):054017. PMID: 19021397.
HARMAN D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956 Jul;11(3):298-300. PMID: 13332224.
Lee HC, Wei YH. Mitochondria and aging. Adv Exp Med Biol. 2012;942:311-27. PMID: 22399429.
Reddy PH. Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer's disease. Exp Neurol. 2009 Aug;218(2):286-92. PMID: 19358844.
Chinopoulos C, Starkov AA, Fiskum G. Cyclosporin A-insensitive permeability transition in brain mitochondria: inhibition by 2-aminoethoxydiphenyl borate. J Biol Chem. 2003 Jul 25;278(30):27382-9. PMID: 12750371.
Ghosh D, LeVault KR, Barnett AJ, Brewer GJ. A reversible early oxidized redox state that precedes macromolecular ROS damage in aging nontransgenic and 3xTg-AD mouse neurons. J Neurosci. 2012 Apr 25;32(17):5821-32. PMID: 22539844.
Scheffler K, Krohn M, Dunkelmann T, Stenzel J, Miroux B, Ibrahim S, von Bohlen Und Halbach O, Heinze HJ, Walker LC, Gsponer JA, Pahnke J. Mitochondrial DNA polymorphisms specifically modify cerebral β-amyloid proteostasis. Acta Neuropathol. 2012 Apr 18. [Epub ahead of print]
Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, Khvorostov I, Spelbrink JN, Wibom R, Jacobs HT, Larsson NG. Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):17993-8. PMID: 16332961.
Liang FQ, Godley BF. Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration. Exp Eye Res. 2003 Apr;76(4):397-403. PMID: 12634104.
Liang FQ, Green L, Wang C, Alssadi R, Godley BF. Melatonin protects human retinal pigment epithelial (RPE) cells against oxidative stress. Exp Eye Res. 2004 Jun;78(6):1069-75. PMID: 15109913.
Ding X, Patel M, Chan CC. Molecular pathology of age-related macular degeneration. Prog Retin Eye Res. 2009 Jan;28(1):1-18. PMID: 19026761.
Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, Yan Y, Wang C, Zhang H, Molkentin JD, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen JX, Yan SD. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med. 2008 Oct;14(10):1097-105. PMID: 18806802.
Manczak M, Park BS, Jung Y, Reddy PH. Differential expression of oxidative phosphorylation genes in patients with Alzheimer's disease: implications for early mitochondrial dysfunction and oxidative damage. Neuromolecular Med. 2004;5(2):147-62. PMID: 15075441.
Xing SL, Chen B, Shen DZ, Zhu CQ. β-amyloid peptide binds and regulates ectopic ATP synthase α-chain on neural surface. Int J Neurosci. 2012 Jun;122(6):290-7. PMID: 22185089.
Rhein V, Baysang G, Rao S, Meier F, Bonert A, Müller-Spahn F, Eckert A. Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells. Cell Mol Neurobiol. 2009 Sep;29(6-7):1063-71. PMID: 19350381.
Hollyfield JG, Bonilha VL, Rayborn ME, Yang X, Shadrach KG, Lu L, Ufret RL, Salomon RG, Perez VL. Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat Med. 2008 Feb;14(2):194-8. PMID: 18223656.
Ramkumar HL, Zhang J, Chan CC. Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD). Prog Retin Eye Res. 2010 May;29(3):169-90. PMID: 20206286.
Wang L, Clark ME, Crossman DK, Kojima K, Messinger JD, Mobley JA, Curcio CA. Abundant lipid and protein components of drusen. PLoS One. 2010 Apr 23;5(4):e10329. PMID: 20428236.
Mullins RF, Russell SR, Anderson DH, Gregory SH. Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. The FASEB Journal. 2000 May;14(7):835-846.
Wang JZ, Wang ZF. Role of melatonin in Alzheimer-like neurodegeneration. Acta Pharmacol Sin. 2006 Jan;27(1):41-9. PMID: 16364209.
Reiss AB, Voloshyna I. Regulation of cerebral cholesterol metabolism in Alzheimer disease. J Investig Med. 2012 Mar;60(3):576-82. PMID: 22367100.
Isas JM, Luibl V, Johnson LV, Kayed R, Wetzel R, Glabe CG, Langen R, Chen J. Soluble and mature amyloid fibrils in drusen deposits. Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1304-10. PMID: 19892876.
Terai K, Iwai A, Kawabata S, Tasaki Y, Watanabe T, Miyata K, Yamaguchi T. beta-amyloid deposits in transgenic mice expressing human beta-amyloid precursor protein have the same characteristics as those in Alzheimer's disease. Neuroscience. 2001;104(2):299-310. PMID: 11377835.
Johnson LV, Leitner WP, Rivest AJ, Staples MK, Radeke MJ, Anderson DH. The Alzheimer's A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11830-5. PMID: 12189211.
Dentchev T, Milam AH, Lee VM, Trojanowski JQ, Dunaief JL. Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas. Mol Vis. 2003 May 14;9:184-90. PMID: 12764254.
Anderson DH, Talaga KC, Rivest AJ, Barron E, Hageman GS, Johnson LV. Characterization of beta amyloid assemblies in drusen: the deposits associated with aging and age-related macular degeneration. Exp Eye Res. 2004 Feb;78(2):243-56. PMID: 14729357.
Barrett PJ, Song Y, Van Horn WD, Hustedt EJ, Schafer JM, Hadziselimovic A, Beel AJ, Sanders CR. The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol. Science. 2012 Jun 1;336(6085):1168-71. PMID: 22654059.
Krishnadev N, Meleth AD, Chew EY. Nutritional supplements for age-related macular degeneration. Curr Opin Ophthalmol. 2010 May;21(3):184-9. PMID: 20216418.
Burstedt MS, Ristoff E, Larsson A, Wachtmeister L. Rod-cone dystrophy with maculopathy in genetic glutathione synthetase deficiency: a morphologic and electrophysiologic study. Ophthalmology. 2009 Feb;116(2):324-31. PMID: 19111905.
Vingolo EM, Pelaia P, Forte R, Rocco M, Giusti C, Rispoli E. Does hyperbaric oxygen (HBO) delivery rescue retinal photoreceptors in retinitis pigmentosa? Doc Ophthalmol. 1998-1999;97(1):33-9. PMID: 10710240.
Berson EL. Light deprivation for early retinitis pigmentosa. A hypothesis. Arch Ophthalmol. 1971 May;85(5):521-9. PMID: 4996600.
Shintani K, Shechtman DL, Gurwood AS. Review and update: current treatment trends for patients with retinitis pigmentosa. Optometry. 2009 Jul;80(7):384-401. PMID: 19545852.
Panfoli I, Calzia D, Ravera S, Morelli AM, Traverso CE. Extra-mitochondrial aerobic metabolism in retinal rod outer segments: new perspectives in retinopathies. Med Hypotheses. 2012 Apr;78(4):423-7. PMID: 22284635.
Imamura H, Nhat KP, Togawa H, Saito K, Iino R, Kato-Yamada Y, Nagai T, Noji H. Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15651-6. PMID: 19720993.
Genova ML, Baracca A, Biondi A, Casalena G, Faccioli M, Falasca AI, Formiggini G, Sgarbi G, Solaini G, Lenaz G. Is supercomplex organization of the respiratory chain required for optimal electron transfer activity? Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):740-6. PMID: 18454935.
Hansford RG, Hogue BA, Mildaziene V. Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age. J Bioenerg Biomembr. 1997 Feb;29(1):89-95. PMID: 9067806.
Jarrett SG, Boulton ME. Consequences of oxidative stress in age-related macular degeneration. Mol Aspects Med. 2012. [Epub ahead of print]
Barnett A, Brewer GJ. Autophagy in aging and Alzheimer's disease: pathologic or protective? J Alzheimers Dis. 2011;25(3):385-94. PMID: 21422527.
Nixon RA, Yang DS. Autophagy failure in Alzheimer's disease--locating the primary defect. Neurobiol Dis. 2011 Jul;43(1):38-45. PMID: 21296668.
Kaarniranta K. Autophagy--hot topic in AMD. Acta Ophthalmol. 2010 Jun;88(4):387-8. PMID: 20353515.
Zhou J, Zhang S, Zhao X, Wei T. Melatonin impairs NADPH oxidase assembly and decreases superoxide anion production in microglia exposed to amyloid-beta1-42. J Pineal Res. 2008 Sep;45(2):157-65. PMID: 18298462.
Mattson MP, Magnus T. Ageing and neuronal vulnerability. Nat Rev Neurosci. 2006 Apr;7(4):278-94. PMID: 16552414.
Koronyo Y, Salumbides BC, Black KL, Koronyo-Hamaoui M. Alzheimer's disease in the retina: imaging retinal aβ plaques for early diagnosis and therapy assessment. Neurodegener Dis. 2012;10(1-4):285-93. PMID: 22343730.
Hoh Kam J, Lenassi E, Jeffery G. Viewing ageing eyes: diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages. PLoS One. 2010 Oct 1;5(10):e13127. PMID: 20957206.
Ding JD, Johnson LV, Herrmann R, Farsiu S, Smith SG, Groelle M, Mace BE, Sullivan P, Jamison JA, Kelly U, Harrabi O, Bollini SS, Dilley J, Kobayashi D, Kuang B, Li W, Pons J, Lin JC, Bowes Rickman C. Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):E279-87. PMID: 21690377.
Dutescu RM, Li QX, Crowston J, Masters CL, Baird PN, Culvenor JG. Amyloid precursor protein processing and retinal pathology in mouse models of Alzheimer's disease. Graefes Arch Clin Exp Ophthalmol. 2009 Sep;247(9):1213-21. PMID: 19271231.
Sarangarajan R, Apte SP. Melanization and phagocytosis: implications for age related macular degeneration. Mol Vis. 2005 Jul 7;11:482-90. PMID: 16030499.
Yoshida T, Ohno-Matsui K, Ichinose S, Sato T, Iwata N, Saido TC, Hisatomi T, Mochizuki M, Morita I. The potential role of amyloid beta in the pathogenesis of age-related macular degeneration. J Clin Invest. 2005 Oct;115(10):2793-800. PMID: 16167083.
Ma W, Lee SE, Guo J, Qu W, Hudson BI, Schmidt AM, Barile GR. RAGE ligand upregulation of VEGF secretion in ARPE-19 cells. Invest Ophthalmol Vis Sci. 2007 Mar;48(3):1355-61. PMID: 17325184.
Wang XC, Zhang YC, Chatterjie N, Grundke-Iqbal I, Iqbal K, Wang JZ. Effect of melatonin and melatonylvalpromide on beta-amyloid and neurofilaments in N2a cells. Neurochem Res. 2008 Jun;33(6):1138-44. PMID: 18231852.
Olcese JM, Cao C, Mori T, Mamcarz MB, Maxwell A, Runfeldt MJ, Wang L, Zhang C, Lin X, Zhang G, Arendash GW. Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease. J Pineal Res. 2009 Aug;47(1):82-96. PMID: 19538338.
Dinet V, An N, Ciccotosto GD, Bruban J, Maoui A, Bellingham SA, Hill AF, Andersen OM, Nykjaer A, Jonet L, Cappai R, Mascarelli F. APP involvement in retinogenesis of mice. Acta Neuropathol. 2011 Mar;121(3):351-63. PMID: 20978902.
Xing SL, Yan J, Yu ZH, Zhu CQ. Neuronal cell surface ATP synthase mediates synthesis of extracellular ATP and regulation of intracellular pH. Cell Biol Int. 2011 Jan;35(1):81-6. PMID: 20626349.
Rattner A, Nathans J. Macular degeneration: recent advances and therapeutic opportunities. Nat Rev Neurosci. 2006 Nov;7(11):860-72. PMID: 17033682.
Panfoli I, Musante L, Bachi A, Ravera S, Calzia D, Cattaneo A, Bruschi M, Bianchini P, Diaspro A, Morelli A, Pepe IM, Tacchetti C, Candiano G. Proteomic analysis of the retinal rod outer segment disks. J Proteome Res. 2008 Jul;7(7):2654-69. PMID: 18489131.
Sergeant N, Wattez A, Galván-valencia M, Ghestem A, David JP, Lemoine J, Sautiére PE, Dachary J, Mazat JP, Michalski JC, Velours J, Mena-López R, Delacourte A. Association of ATP synthase alpha-chain with neurofibrillary degeneration in Alzheimer's disease. Neuroscience. 2003;117(2):293-303. PMID: 12614671.
Acuña Castroviejo D, López LC, Escames G, López A, GarcÃa JA, Reiter RJ. Melatonin-mitochondria interplay in health and disease. Curr Top Med Chem. 2011;11(2):221-40. Review. PubMed PMID: 21244359.
Pagani L, Eckert A. Amyloid-Beta interaction with mitochondria. Int J Alzheimers Dis. 2011 Mar 15;2011:925050. PMID: 21461357.
Schmidt C, Lepsverdize E, Chi SL, Das AM, Pizzo SV, Dityatev A, Schachner M. Amyloid precursor protein and amyloid beta-peptide bind to ATP synthase and regulate its activity at the surface of neural cells. Mol Psychiatry. 2008 Oct;13(10):953-69. PMID: 17726461.
Quinn J, Kulhanek D, Nowlin J, Jones R, Praticò D, Rokach J, Stackman R. Chronic melatonin therapy fails to alter amyloid burden or oxidative damage in old Tg2576 mice: implications for clinical trials. Brain Res. 2005 Mar 10;1037(1-2):209-13. PMID: 15777772.
Lahiri DK, Chen D, Ge YW, Bondy SC, Sharman EH. Dietary supplementation with melatonin reduces levels of amyloid beta-peptides in the murine cerebral cortex. J Pineal Res. 2004 May;36(4):224-31. PMID: 15066046.
Matsubara E, Bryant-Thomas T, Pacheco Quinto J, Henry TL, Poeggeler B, Herbert D, Cruz-Sanchez F, Chyan YJ, Smith MA, Perry G, Shoji M, Abe K, Leone A, Grundke-Ikbal I, Wilson GL, Ghiso J, Williams C, Refolo LM, Pappolla MA, Chain DG, Neria E. Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease. J Neurochem. 2003 Jun;85(5):1101-8. Erratum in: J Neurochem. 2003 Sep;86(5):1312. PMID: 12753069.
Arias-Esparza M, Arias R, Arias P, Arias M, SolÃs-Herrera A. The Unexpected Capability of Melanin to Split the Water Molecule and the Alzheimer’s Disease. Neuroscience & Medicine. 2011;2(3):217-221.
Herrera AS, Esparza MDCA, Esquivel JJA, LandÃn G, Miranda RISA, Arias PES, Arias MPS. The Pharmacologic Intensification of the Water Dissociation Process, or Human Photosynthesis, and Its Effect over the Recovery Mechanisms in Tissues Affected by Bloodshed of Diverse Etiology. International Journal of Clinical Medicine. 2011;2(3):332-338.
Acuna-Castroviejo D, Escames G, Rodriguez MI, Lopez LC. Melatonin role in the mitochondrial function. Front Biosci. 2007 Jan 1;12:947-63.PMID: 17127351.
Rastmanesh R. Potential of melatonin to treat or prevent age-related macular degeneration through stimulation of telomerase activity. Med Hypotheses. 2011 Jan;76(1):79-85. PMID: 20884126.
Hardeland R. Melatonin, Mitochondrial Electron Flux and Leakage: Recent Findings and Resolution of Contradictory Results. Adv Stud Biol. 2009;1(5):207–230.
Pappolla M, Bozner P, Soto C, Shao H, Robakis NK, Zagorski M, Frangione B, Ghiso J. Inhibition of Alzheimer beta-fibrillogenesis by melatonin. J Biol Chem. 1998 Mar 27;273(13):7185-8. PMID: 9516407.
Poeggeler B, Miravalle L, Zagorski MG, Wisniewski T, Chyan YJ, Zhang Y, Shao H, Bryant-Thomas T, Vidal R, Frangione B, Ghiso J, Pappolla MA. Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the Alzheimer amyloid Abeta peptide. Biochemistry. 2001 Dec 11;40(49):14995-5001. PMID: 11732920.
Savaskan E, Ayoub MA, Ravid R, Angeloni D, Fraschini F, Meier F, Eckert A, Müller-Spahn F, Jockers R. Reduced hippocampal MT2 melatonin receptor expression in Alzheimer's disease. J Pineal Res. 2005 Jan;38(1):10-6. PMID: 15617532.
Pappolla MA, Simovich MJ, Bryant-Thomas T, Chyan YJ, Poeggeler B, Dubocovich M, Bick R, Perry G, Cruz-Sanchez F, Smith MA. The neuroprotective activities of melatonin against the Alzheimer beta-protein are not mediated by melatonin membrane receptors. J Pineal Res. 2002 Apr;32(3):135-42. PMID: 12074096.
Baba K, Pozdeyev N, Mazzoni F, Contreras-Alcantara S, Liu C, Kasamatsu M, Martinez-Merlos T, Strettoi E, Michael Iuvone P, Tosini G. Melatonin modulates visual function and cell viability in the mouse retina via the MT1 melatonin receptor. Proc Natl Acad Sci U S A. 2009 June 30;106(35):15043-8.
Slominski A. Neuroendocrine activity of the melanocyte. Exp Dermatol. 2009 Sep;18(9):760-3. PMID: 19558501.
Kurakin A. The self-organizing fractal theory as a universal discovery method: the phenomenon of life. Theor Biol Med Model. 2011 Mar 29;8:4. PMID: 21447162.
Olsen S, Riesz J, Mahadevan I, Coutts A, Bothma JP, Powell BJ, McKenzie RH, Smith SC, Meredith P. Convergent Proton-Transfer Photocycles Violate Mirror-Image Symmetry in a Key Melanin Monomer. J Am Chem Soc. 2007;129(21):6672-3.
Dadachova E, Casadevall A. Ionizing radiation: how fungi cope, adapt, and exploit with the help of melanin. Curr Opin Microbiol. 2008 Dec;11(6):525-31. PMID: 18848901.
Khandhadia S, Lotery A. Oxidation and age-related macular degeneration: insights from molecular biology. Expert Rev Mol Med. 2010 Oct 20;12:e34. PMID: 20959033.
Morelli A, Ravera S, Panfoli I. Hypothesis of an energetic function for myelin. Cell Biochem Biophys. 2011 Sep;61(1):179-87. PMID: 21455684.
Bürklen TS, Schlattner U, Homayouni R, Gough K, Rak M, Szeghalmi A, Wallimann T. The creatine kinase/creatine connection to Alzheimer's disease: CK-inactivation, APP-CK complexes and focal creatine deposits. J Biomed Biotechnol. 2006;2006(3):35936. PMID: 17047305.
- Abstract Viewed: 4114 times
- Full text PDF Downloaded: 3778 times
