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Cited by 67Alzheimer's disease research and treatmentsAluminum toxicity and tolerance in plants and animalsCholinesterase and Neurodegenerative Diseases

Role of Metal Cations of Copper, Iron, and Aluminum and Multifunctional Ligands in Alzheimer’s Disease: Experimental and Computational Insights

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Puentes-Díaz, Nicolás, Chaparro, Diego, Morales-Morales, David, Flores-Gaspar, Areli, Alí-Torres, Jorge·2023·ACS Omega
DOI 10.1021/acsomega.2c06939PMC PMC9909689
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Abstract

Alzheimer's disease (AD) is the most common form of dementia, affecting millions of people around the world. Even though the causes of AD are not completely understood due to its multifactorial nature, some neuropathological hallmarks of its development have been related to the high concentration of some metal cations. These roles include the participation of these metal cations in the production of reactive oxygen species, which have been involved in neuronal damage. In order to avoid the increment in the oxidative stress, multifunctional ligands used to coordinate these metal cations have been proposed as a possible treatment to AD. In this review, we present the recent advances in experimental and computational works aiming to understand the role of two redox active and essential transition-metal cations (Cu and Fe) and one nonbiological metal (Al) and the recent proposals on the development of multifunctional ligands to stop or revert the damaging effects promoted by these metal cations.

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  • Excess intracellular Fe2+ catalyzes the Fenton reaction, generating hydroxyl radicals that cause lipid peroxidation, DNA damage, and protein oxidation.

    “Excess intracellular Fe2⁺ catalyzes the Fenton reaction, generating hydroxyl radicals that cause lipid peroxidation, DNA damage, and protein oxidation [108].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [108]

    The “Oxidative Stress in AD” section (page unavailable) says free iron cations produce ROS through Fenton reactions and that excess ROS can damage lipids, proteins, and DNA. It does not specifically state that excess intracellular Fe²⁺ generates hydroxyl radicals through this reaction or directly attribute all three forms of damage to those radicals. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The resulting oxidative stress can destabilize iron-containing proteins, releasing more free iron and amplifying injury.

    “The resulting oxidative stress can destabilize iron-containing proteins, releasing more free iron and amplifying injury.”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [108]

    The “Oxidative Stress in AD” section says ROS can damage proteins and that free iron can generate ROS, contributing to a toxic cycle. It does not say oxidative stress destabilizes iron-containing proteins or releases iron from them, so the claimed mechanism is unsupported. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Iron overload can trigger ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation and mitochondrial shrinkage.

    “Moreover, iron overload can trigger ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation and mitochondrial shrinkage [108].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [108]

    The “Oxidative Stress in AD” section (page unavailable) links pathological iron levels to mitochondrial dysfunction and says iron-generated reactive oxygen species can damage lipids. It does not identify ferroptosis as the resulting cell-death mechanism or describe mitochondrial shrinkage; searches for those terms found no supporting passage. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 196

  1. 2022 Alzheimer’s Disease Facts and Figures. In Alzheimer’s & Dementia, 2022, 18, ((4),), 700– 789. 10.1002/alz.12638 35289055 · DOI
  2. Ramesh M.; Govindaraju T. Multipronged Diagnostic and Therapeutic Strategies for Alzheimer’s Disease. Chem. Sci. 2022, 13 (46), 13657– 13689. 10.1039/D2SC03932J. 36544728 PMC9710308 · DOI
  3. Kim A.; Lim S.; Kim Y. Metal Ion Effects on Aβ and Tau Aggregation. Int. J. Mol. Sci. 2018, 19 (1), 128 10.3390/ijms19010128. 29301328 PMC5796077 · DOI
  4. Di Natale G.; Sabatino G.; Sciacca M. F. M.; Tosto R.; Milardi D.; Pappalardo G. Aβ and Tau Interact with Metal Ions, Lipid Membranes and Peptide-Based Amyloid Inhibitors: Are These Common Features Relevant in Alzheimer’s Disease?. Molecules 2022, 27 (16), 5066 10.3390/molecules27165066. 36014310 PMC9414153 · DOI
  5. Alies B.; Sasaki I.; Proux O.; Sayen S.; Guillon E.; Faller P.; Hureau C. Zn Impacts Cu Coordination to Amyloid-β, the Alzheimer’s Peptide, but Not the ROS Production and the Associated Cell Toxicity. Chem. Commun. 2013, 49 (12), 1214 10.1039/c2cc38236a. 23282470 · DOI
  6. Selkoe D. J. Folding Proteins in Fatal Ways. Nature 2003, 426 (6968), 900– 904. 10.1038/nature02264. 14685251 · DOI
  7. Rauk A. The Chemistry of Alzheimer’s Disease. Chem. Soc. Rev. 2009, 38 (9), 2698– 2715. 10.1039/b807980n. 19690748 · DOI · Paper page
  8. Wilquet V.; Strooper B. De. Amyloid-Beta Precursor Protein Processing in Neurodegeneration. Curr. Opin. Neurobiol. 2004, 14 (5), 582– 588. 10.1016/j.conb.2004.08.001. 15464891 · DOI
  9. Selkoe D. J. Alzheimer’s Disease Is a Synaptic Failure. Science (80-.) 2002, 298 (5594), 789– 791. 10.1126/science.1074069. 12399581 · DOI · Paper page
  10. Kim H.-J.; Chae S.-C.; Lee D.-K.; Chromy B.; et al. Selective Neuronal Degeneration Induced by Soluble Oligomeric Amyloid Beta Protein. FASEB J. 2003, 17 (1), 118– 120. 10.1096/fj.01-0987fje. 12424218 · DOI
  11. Bishop G. M.; Robinson S. R. Physiological Roles of Amyloid-β and Implications for Its Removal in Alzheimer’s Disease. Drugs and Aging 2004, 21 (10), 621– 630. 10.2165/00002512-200421100-00001. 15287821 · DOI · Paper page
  12. Alí-Torres J.; Mirats A.; Maréchal J. D.; Rodríguez-Santiago L.; Sodupe M. 3D Structures and Redox Potentials of Cu2+-Aβ(1–16) Complexes at Different PH: A Computational Study. J. Phys. Chem. B 2014, 118 (18), 4840– 4850. 10.1021/jp5019718. 24738872 · DOI
  13. White A. R.; Reyes R.; Mercer J. F. B.; Camakaris J.; Zheng H.; Bush A. I.; Multhaup G.; Beyreuther K.; Masters C. L.; Cappai R. Copper Levels Are Increased in the Cerebral Cortex and Liver of APP and APLP2 Knockout Mice. Brain Res. 1999, 842 (2), 439– 444. 10.1016/S0006-8993(99)01861-2. 10526140 · DOI
  14. Rajasekhar K.; Chakrabarti M.; Govindaraju T. Function and Toxicity of Amyloid Beta and Recent Therapeutic Interventions Targeting Amyloid Beta in Alzheimer’s Disease. Chem. Commun. 2015, 51 (70), 13434– 13450. 10.1039/C5CC05264E. 26247608 · DOI
  15. Panza F.; Lozupone M.; Logroscino G.; Imbimbo B. P. A Critical Appraisal of Amyloid-β-Targeting Therapies for Alzheimer Disease. Nat. Rev. Neurol. 2019, 15 (2), 73– 88. 10.1038/s41582-018-0116-6. 30610216 · DOI · Paper page
  16. Panza F.; Lozupone M.; Seripa D.; Imbimbo B. P. Amyloid-β Immunotherapy for Alzheimer Disease: Is It Now a Long Shot?. Ann. Neurol. 2019, 85 (3), 303– 315. 10.1002/ana.25410. 30635926 · DOI · Paper page
  17. Loureiro J. C.; Pais M. V.; Stella F.; Radanovic M.; Teixeira A. L.; Forlenza O. V.; De Souza L. C. Passive Antiamyloid Immunotherapy for Alzheimer’s Disease. Curr. Opin. Psychiatry 2020, 33 (3), 284– 291. 10.1097/YCO.0000000000000587. 32040044 · DOI
  18. Neve R. L.; Robakis N. K. Alzheimer’s Disease: A Re-Examination of the Amyloid Hypothesis. Trends Neurosci 1998, 21 (1), 15– 19. 10.1016/S0166-2236(97)01168-5. 9464679 · DOI
  19. Salim S. Oxidative Stress and the Central Nervous System. J. Pharmacol. Exp. Ther. 2017, 360 (1), 201– 205. 10.1124/jpet.116.237503. 27754930 PMC5193071 · DOI
  20. Campian J. L.; Qian M.; Gao X.; Eaton J. W. Oxygen Tolerance and Coupling of Mitochondrial Electron Transport. J. Biol. Chem. 2004, 279 (45), 46580– 46587. 10.1074/jbc.M406685200. 15328348 · DOI
  21. Turrens J. F. Mitochondrial Formation of Reactive Oxygen Species. J. Physiol. 2003, 552 (2), 335– 344. 10.1113/jphysiol.2003.049478. 14561818 PMC2343396 · DOI · Paper page
  22. Brand M. D. Mitochondrial Generation of Superoxide and Hydrogen Peroxide as the Source of Mitochondrial Redox Signaling. Free Radic. Biol. Med. 2016, 100, 14– 31. 10.1016/j.freeradbiomed.2016.04.001. 27085844 · DOI · Paper page
  23. Zhou X.; Zhuang Z.; Wang W.; He L.; Wu H.; Cao Y.; Pan F.; Zhao J.; Hu Z.; Sekhar C.; Guo Z. OGG1 Is Essential in Oxidative Stress Induced DNA Demethylation. Cell. Signal. 2016, 28 (9), 1163– 1171. 10.1016/j.cellsig.2016.05.021. 27251462 · DOI
  24. Sharma P.; Jha A. B.; Dubey R. S.; Pessarakli M. Reactive Oxygen Species, Oxidative Damage, and Antioxidative Defense Mechanism in Plants under Stressful Conditions. J. Bot. 2012, 2012, 1– 26. 10.1155/2012/217037. · DOI
  25. Dietz K.-J.; Baier M.; Krämer U. Free Radicals and Reactive Oxygen Species as Mediators of Heavy Metal Toxicity in Plants. Heavy Met. Stress Plants 1999, 73– 97. 10.1007/978-3-662-07745-0_4. · DOI
  26. Jomova K.; Valko M. Advances in Metal-Induced Oxidative Stress and Human Disease. Toxicology 2011, 283 (2–3), 65– 87. 10.1016/j.tox.2011.03.001. 21414382 · DOI
  27. Hippeli S.; Elstner E. F. Transition Metal Ion-Catalysed Oxygen Activation during Pathogenic Processes. FEBS Lett. 1999, 443 (1), 1– 7. 10.1016/S0014-5793(98)01665-2. 9928941 · DOI
  28. Jomova K.; Baros S.; Valko M. Redox Active Metal-Induced Oxidative Stress in Biological Systems. Transit. Met. Chem. 2012, 37 (2), 127– 134. 10.1007/s11243-012-9583-6. · DOI
  29. Chevion M.; Berenshtein E.; Zhu B.-Z. The Role of Transition Metal Ions in Free Radical-Mediated Damage. React. Oxyg. Species Biol. Syst. 2002, 103– 131. 10.1007/0-306-46806-9_4. · DOI
  30. Prousek J. Fenton Chemistry in Biology and Medicine. Pure Appl. Chem. 2007, 79 (12), 2325– 2338. 10.1351/pac200779122325. · DOI
  31. Liochev S. I.; Fridovich I. The Haber-Weiss Cycle - 70 Years Later: An Alternative View. Redox Rep 2002, 7 (1), 55– 57. 10.1179/135100002125000190. 11981456 · DOI
  32. Shen J.; Griffiths P. T.; Campbell S. J.; Utinger B.; Kalberer M.; Paulson S. E. Ascorbate Oxidation by Iron, Copper and Reactive Oxygen Species: Review, Model Development, and Derivation of Key Rate Constants. Sci. Rep. 2021, 11 (1), 1– 14. 10.1038/s41598-021-86477-8. 33795736 PMC8016884 · DOI
  33. Dikalov S. I.; Vitek M. P.; Mason R. P. Cupric-Amyloid β Peptide Complex Stimulates Oxidation of Ascorbate and Generation of Hydroxyl Radical. Free Radic. Biol. Med. 2004, 36 (3), 340– 347. 10.1016/j.freeradbiomed.2003.11.004. 15036353 · DOI
  34. Núñez M. T.; Hidalgo C. Noxious Iron–Calcium Connections in Neurodegeneration. Front. Neurosci. 2019, 13. 10.3389/fnins.2019.00048. PMC6379295 30809110 · DOI
  35. Green D. R.; Goldstein J. C.; Waterhouse N. J.; Juin P.; Evan G. I. The Coordinate Release of Cytochrome: C: During Apoptosis Is Rapid, Complete and Kinetically Invariant: Article: Nature Cell Biology. Nat. Cell Biol. 2000, 2 (3), 156– 162. 10.1038/35004029. 10707086 · DOI
  36. Mirats A.; Alí-Torres J.; Rodríguez-Santiago L.; Sodupe M.; La Penna G. Dioxygen Activation in Cu-Amyloid β Complex. Phys. Chem. Chem. Phys. 2015, 17 (41), 27270– 27274. 10.1039/C5CP04025F. 26427541 · DOI
  37. Mirats A.; Alí-Torres J.; Rodríguez-Santiago L.; Sodupe M. Stability of Transient Cu+Aβ (1–16) Species and Influence of Coordination and Peptide Configuration on Superoxide Formation. Theor. Chem. Acc. 2016, 135 (3), 1– 9. 10.1007/s00214-016-1836-6. · DOI
  38. Nguyen M.; Huang M.; Liu Y.; Meunier B.; Robert A. Is Iron Associated with Amyloid Involved in the Oxidative Stress of Alzheimer’s Disease?. Comptes Rendus Chim 2017, 20 (11–12), 987– 989. 10.1016/j.crci.2017.07.009. · DOI
  39. Guo Q.; Sopher B. L.; Furukawa K.; Pham D. G.; Robinson N.; Martin G. M.; Mattson M. P. Alzheimer’s Presenilin Mutation Sensitizes Neural Cells to Apoptosis Induced by Trophic Factor Withdrawal and Amyloid β-Peptide: Involvement of Calcium and Oxyradicals. J. Neurosci. 1997, 17 (11), 4212– 4222. 10.1523/JNEUROSCI.17-11-04212.1997. 9151738 PMC6573527 · DOI
  40. Marques C. A.; Keil U.; Bonert A.; Steiner B.; Haass C.; Müller W. E.; Eckert A. Neurotoxic Mechanisms Caused by the Alzheimer’s Disease-Linked Swedish Amyloid Precursor Protein. Mutation Oxidative Stress, Caspases, and the JNK Pathway. J. Biol. Chem. 2003, 278 (30), 28294– 28302. 10.1074/jbc.M212265200. 12730216 · DOI
  41. Eckert A.; Steiner B.; Marques C.; Leutz S.; Romig H.; Haass C.; Müller W. E. Elevated Vulnerability to Oxidative Stress-Induced Cell Death and Activation of Caspase-3 by the Swedish Amyloid Precursor Protein Mutation. J. Neurosci. Res. 2001, 64 (2), 183– 192. 10.1002/jnr.1064. 11288146 · DOI
  42. Smith M. A.; Hirai K.; Hsiao K.; Pappolla M. A.; Harris P. L. R.; Siedlak S. L.; Tabaton M.; Perry G. Amyloid-β Deposition in Alzheimer Transgenic Mice Is Associated with Oxidative Stress. J. Neurochem. 1998, 70 (5), 2212– 2215. 10.1046/j.1471-4159.1998.70052212.x. 9572310 · DOI
  43. LaFontaine M. A.; Mattson M. P.; Butterfield D. A. Oxidative Stress in Synaptosomal Proteins from Mutant Presenilin-1 Knock-in Mice: Implications for Familial Alzheimer’s Disease. Neurochem. Res. 2002, 27 (5), 417– 421. 10.1023/A:1015560116208. 12064358 · DOI
  44. Schuessel K.; Frey C.; Jourdan C.; Keil U.; Weber C. C.; Müller-Spahn F.; Müller W. E.; Eckert A. Aging Sensitizes toward ROS Formation and Lipid Peroxidation in PS1M146L Transgenic Mice. Free Radic. Biol. Med. 2006, 40 (5), 850– 862. 10.1016/j.freeradbiomed.2005.10.041. 16520237 · DOI
  45. Bogdanovic N.; Zilmer M.; Zilmer K.; Rehema A.; Karelson E. The Swedish APP670/671 Alzheimer ’ s Disease Mutation: The First Evidence for Strikingly Increased Oxidative Injury in the Temporal. Dement Geriatr Cogn Discord 2001, 12, 364– 370. 10.1159/000051282. 11598307 · DOI
  46. Leibson C. L.; Rocca W. A.; Hanson V. A.; Cha R.; Kokmen E.; O’Brien P. C.; Palumbo P. J. Risk of Dementia among Persons with Diabetes Mellitus: A Population- Based Cohort Study. Am. J. Epidemiol. 1997, 145 (4), 301– 308. 10.1093/oxfordjournals.aje.a009106. 9054233 · DOI · Paper page
  47. Guo Z.; Cupples L. A.; Kurz A.; Auerbach S. H.; Volicer L.; Chui H.; Green R. C.; Sadovnick A. D.; Duara R.; DeCarli C.; Johnson K.; Go R. C.; Growdon J. H.; Haines J. L.; Kukull W. A.; Farrer L. A. Head Injury and the Risk of AD in the MIRAGE Study. Neurology 2000, 54 (6), 1316– 1323. 10.1212/WNL.54.6.1316. 10746604 · DOI · Paper page
  48. Kivipelto M.; Helkala E. L.; Laakso M. P.; Hänninen T.; Hallikainen M.; Alhainen K.; Iivonen S.; Mannermaa A.; Tuomilehto J.; Nissinen A.; Soininen H. Apolipoprotein E Ε4 Allele, Elevated Midlife Total Cholesterol Level, and High Midlife Systolic Blood Pressure Are Independent Risk Factors for Late-Life Alzheimer Disease. Ann. Int. Med. 2002, 137 (3), 149– 155. 10.7326/0003-4819-137-3-200208060-00006. 12160362 · DOI
  49. Honig L. S.; Tang M.-X.; Albert S.; Costa R.; Luchsinger J.; Manly Md.; Stern Y.; Mayeux R. Stroke and the Risk of Alzheimer Disease-Correction. Arch. Neurol. 2004, 61 (3), 368 10.1001/archneur.61.3.368. 14676044 · DOI
  50. Foley D. J.; White L. R. Dietary Intake of Antioxidants and Risk of Alzheimer Disease: Food for Thought. J. Am. Med. Assoc. 2002, 287 (24), 3261– 3263. 10.1001/jama.287.24.3261. 12076225 · DOI
  51. Morris M. C.; Evans D. A.; Bienias J. L.; Tangney C. C.; Bennett D. A.; Wilson R. S.; Aggarwal N.; Schneider J. Consumption of Fish and N-3 Fatty Acids and Risk of Incident Alzheimer Disease. Arch. Neurol. 2003, 60 (7), 940– 946. 10.1001/archneur.60.7.940. 12873849 · DOI · Paper page
  52. Truelsen T.; Thudium D.; Grønbæk M. Amount and Type of Alcohol and Risk of Dementia. Neurology 2002, 59, 1313– 1319. 10.1212/01.WNL.0000031421.50369.E7. 12427876 · DOI
  53. Sung S.; Yao Y.; Uryu K.; Yang H.; Lee V. M. Y.; Trojanowski J. Q.; Praticò D. Early Vitamin E Supplementation in Young but Not Aged Mice Reduces Abeta Levels and Amyloid Deposition in a Transgenic Model of Alzheimer’s Disease. FASEB J. 2004, 18 (2), 323– 325. 10.1096/fj.03-0961fje. 14656990 · DOI
  54. Nunomura A.; Perry G.; Aliev G.; Hirai K.; Takeda A.; Balraj E. K.; Jones P. K.; Ghanbari H.; Wataya T.; Shimohama S.; Chiba S.; Atwood C. S.; Petersen R. B.; Smith M. A. Oxidative Damage Is the Earliest Event in Alzheimer Disease. J. Neuropathol. Exp. Neurol. 2001, 60 (8), 759– 767. 10.1093/jnen/60.8.759. 11487050 · DOI · Paper page
  55. Nunomura A.; Perry G.; Pappolla M. A.; Wade R.; Hirai K.; Chiba S.; Smith M. A. RNA Oxidation Is a Prominent Feature of Vulnerable Neurons in Alzheimer’s Disease. J. Neurosci. 1999, 19 (6), 1959– 1964. 10.1523/JNEUROSCI.19-06-01959.1999. 10066249 PMC6782583 · DOI
  56. Nunomura A.; Chiba S.; Lippa C. F.; Cras P.; Kalaria R. N.; Takeda A.; Honda K.; Smith M. A.; Perry G. Neuronal RNA Oxidation Is a Prominent Feature of Familial Alzheimer’s Disease. Neurobiol. Dis. 2004, 17 (1), 108– 113. 10.1016/j.nbd.2004.06.003. 15350971 · DOI
  57. Drake J.; Link C. D.; Butterfield D. A. Oxidative Stress Precedes Fibrillar Deposition of Alzheimer’s Disease Amyloid β-Peptide (1–42) in a Transgenic Caenorhabditis Elegans Model. Neurobiol. Aging 2003, 24 (3), 415– 420. 10.1016/S0197-4580(02)00225-7. 12600717 · DOI · Paper page
  58. Zou K.; Gong J. S.; Yanagisawa K.; Michikawa M. A Novel Function of Monomeric Amyloid β-Protein Serving as an Antioxidant Molecule against Metal-Induced Oxidative Damage. J. Neurosci. 2002, 22 (12), 4833– 4841. 10.1523/JNEUROSCI.22-12-04833.2002. 12077180 PMC6757724 · DOI · Paper page
  59. Smith M. A.; Nunomura A.; Zhu X.; Takeda A.; Perry G. Metabolic, Metallic, and Mitotic Sources of Oxidative Stress in Alzheimer Disease. Antioxid. Redox Signal. 2000, 2 (3), 413– 420. 10.1089/15230860050192198. 11229355 · DOI
  60. Giacobini E. Cholinesterase Inhibitors Stabilize Alzheimer’s Disease. Ann. N.Y. Acad. Sci. 2000, 920, 321– 327. 10.1111/j.1749-6632.2000.tb06942.x. 11193171 · DOI
  61. Parsons C. G.; Stöffler A.; Danysz W. Memantine: A NMDA Receptor Antagonist That Improves Memory by Restoration of Homeostasis in the Glutamatergic System - Too Little Activation Is Bad, Too Much Is Even Worse. Neuropharmacology 2007, 53 (6), 699– 723. 10.1016/j.neuropharm.2007.07.013. 17904591 · DOI
  62. Adlard P. A.; Bush A. I. Metals and Alzheimer’s Disease: How Far Have We Come in the Clinic?. J. Alzheimer's Dis. 2018, 62 (3), 1369– 1379. 10.3233/JAD-170662. 29562528 PMC5870044 · DOI
  63. Mezzaroba L.; Alfieri D. F.; Colado Simão A. N.; Vissoci Reiche E. M. The Role of Zinc, Copper, Manganese and Iron in Neurodegenerative Diseases. Neurotoxicology 2019, 74 (March), 230– 241. 10.1016/j.neuro.2019.07.007. 31377220 · DOI · Paper page
  64. Bush A. I.; Curtain C. C. Twenty Years of Metallo-Neurobiology: Where to Now?. Eur. Biophys. J. 2008, 37 (3), 241– 245. 10.1007/s00249-007-0228-1. 17994233 · DOI
  65. Bush A. I. Drug Development Based on the Metals Hypothesis of Alzheimer’s Disease. J. Alzheimer's Dis. 2008, 15 (2), 223– 240. 10.3233/JAD-2008-15208. 18953111 · DOI
  66. del Barrio M.; Borghesani V.; Hureau C.; Faller P. Metal-Binding to Amyloid-β Peptide: Coordination, Aggregation, and Reactive Oxygen Species Production. In Biometals in Neurodegenerative Diseases; Elsevier, 2017; pp 265– 281. 10.1016/B978-0-12-804562-6.00014-2. · DOI
  67. Hung Y. H.; Bush A. I.; Cherny R. A. Copper in the Brain and Alzheimer’s Disease. J. Biol. Inorg. Chem. 2010, 15 (1), 61– 76. 10.1007/s00775-009-0600-y. 19862561 · DOI
  68. Valko M.; Morris H.; Cronin M. T. Metals, toxicity and oxidative stress. Curr. Med. Chem. 2005, 12, 1161– 1208. 10.2174/0929867053764635. 15892631 · DOI · Paper page
  69. Bost M.; Houdart S.; Oberli M.; Kalonji E.; Huneau J. F.; Margaritis I. Dietary Copper and Human Health: Current Evidence and Unresolved Issues. J. Trace Elem. Med. Biol. 2016, 35, 107– 115. 10.1016/j.jtemb.2016.02.006. 27049134 · DOI
  70. Davies K. M.; Hare D. J.; Cottam V.; Chen N.; Hilgers L.; Halliday G.; Mercer J. F. B.; Double K. L. Localization of Copper and Copper Transporters in the Human Brain. Metallomics 2013, 5 (1), 43– 51. 10.1039/C2MT20151H. 23076575 · DOI
  71. Xiao T.; Ackerman C. M.; Carroll E. C.; Jia S.; Hoagland A.; Chan J.; Thai B.; Liu C. S.; Isacoff E. Y.; Chang C. J. Copper Regulates Rest-Activity Cycles through the Locus Coeruleus-Norepinephrine System. Nat. Chem. Biol. 2018, 14 (7), 655– 663. 10.1038/s41589-018-0062-z. 29867144 PMC6008210 · DOI
  72. Rae D.; Schmidt P. J.; Pufahl R. A.; Culotta V. C.; O’Halloran T. V. Undetectable Intracellular Free Copper: The Requirement of a Copper Caperone for Superoxide Dismutase. Science 1999, 284, 805– 808. 10.1126/science.284.5415.805. 10221913 · DOI
  73. Lanza V.; Travaglia A.; Malgieri G.; Fattorusso R.; Grasso G.; Di Natale G.; Zito V.; Arena G.; Milardi D.; Rizzarelli E. Ubiquitin Associates with the N-Terminal Domain of Nerve Growth Factor: The Role of Copper(II) Ions. Chem. - A Eur. J. 2016, 22 (49), 17767– 17775. 10.1002/chem.201603650. 27759905 · DOI
  74. Speisky H.; Gómez M.; Carrasco-Pozo C.; Pastene E.; Lopez-Alarcón C.; Olea-Azar C. Cu(I)-Glutathione Complex: A Potential Source of Superoxide Radicals Generation. Bioorg. Med. Chem. 2008, 16 (13), 6568– 6574. 10.1016/j.bmc.2008.05.026. 18515117 · DOI
  75. Speisky H.; Gómez M.; Burgos-Bravo F.; López-Alarcón C.; Jullian C.; Olea-Azar C.; Aliaga M. E. Generation of Superoxide Radicals by Copper-Glutathione Complexes: Redox-Consequences Associated with Their Interaction with Reduced Glutathione. Bioorg. Med. Chem. 2009, 17 (5), 1803– 1810. 10.1016/j.bmc.2009.01.069. 19230679 · DOI
  76. Matheou C. J.; Younan N. D.; Viles J. H. Cu2+ Accentuates Distinct Misfolding of Aβ(1–40) and Aβ(1–42) Peptides, and Potentiates Membrane Disruption. Biochem. J. 2015, 466, 233– 242. 10.1042/BJ20141168. 25471541 · DOI
  77. Sparks D. L.; Schreurs B. G. Trace Amounts of Copper in Water Induce β-Amyloid Plaques and Learning Deficits in a Rabbit Model of Alzheimer’s Disease. Proc. Natl. Acad. Sci. U. S. A. 2003, 100 (19), 11065– 11069. 10.1073/pnas.1832769100. 12920183 PMC196927 · DOI
  78. Xu J.; Church S. J.; Patassini S.; Begley P.; Waldvogel H. J.; Curtis M. A.; Faull R. L. M.; Unwin R. D.; Cooper G. J. S. Evidence for Widespread, Severe Brain Copper Deficiency in Alzheimer’s Dementia. Metallomics 2017, 9 (8), 1106– 1119. 10.1039/C7MT00074J. 28654115 · DOI
  79. Kaden D.; Bush A. I.; Danzeisen R.; Bayer T. A.; Multhaup G. Disturbed Copper Bioavailability in Alzheimer’s Disease. Int. J. Alzheimers. Dis. 2011, 2011 (II), 1 10.4061/2011/345614. PMC3227474 22145082 · DOI
  80. Bellingham S. A.; Lahiri D. K.; Maloney B.; La Fontaine S.; Multhaup G.; Camakaris J. Copper Depletion Down-Regulates Expression of the Alzheimer’s Disease Amyloid-β Precursor Protein Gene. J. Biol. Chem. 2004, 279 (19), 20378– 20386. 10.1074/jbc.M400805200. 14985339 · DOI
  81. Cater M. A.; McInnes K. T.; Li Q.-X.; Volitakis I.; La Fontaine S.; Mercer J. F. B.; Bush A. I. Intracellular Copper Deficiency Increases Amyloid-β Secretion by Diverse Mechanisms. Biochem. J. 2008, 412 (1), 141– 152. 10.1042/BJ20080103. 18248325 · DOI
  82. Raffa D. F.; Gómez-Balderas R.; Brunelle P.; Rickard G. A.; Rauk A. Ab Initio Model Studies of Copper Binding to Peptides Containing a His-His Sequence: Relevance to the β-Amyloid Peptide of Alzheimer’s Disease. J. Biol. Inorg. Chem. 2005, 10 (8), 887– 902. 10.1007/s00775-005-0038-9. 16267663 · DOI
  83. Rickard G. A.; Gomez-Balderas R.; Brunelle P.; Raffa D. F.; Rauk A. Binding Affinities for Models of Biologically Available Potential Cu(II) Ligands Relevant to Alzheimer’s Disease: An Ab Initio Study. J. Phys. Chem. A 2005, 109 (37), 8361– 8370. 10.1021/jp052303r. 16834228 · DOI
  84. Strodel B.; Coskuner-Weber O. Transition Metal Ion Interactions with Disordered Amyloid-β Peptides in the Pathogenesis of Alzheimer’s Disease: Insights from Computational Chemistry Studies. J. Chem. Inf. Model. 2019, 59 (5), 1782– 1805. 10.1021/acs.jcim.8b00983. 30933519 · DOI
  85. Drew S. C.; Barnham K. J. The Heterogeneous Nature of Cu2+ Interactions with Alzheimer’s Amyloid-β Peptide. Acc. Chem. Res. 2011, 44 (11), 1146– 1155. 10.1021/ar200014u. 21714485 · DOI
  86. Atrián-Blasco E.; Gonzalez P.; Santoro A.; Alies B.; Faller P.; Hureau C. Cu and Zn Coordination to Amyloid Peptides: From Fascinating Chemistry to Debated Pathological Relevance. Coord. Chem. Rev. 2018, 371, 38– 55. 10.1016/j.ccr.2018.04.007. PMC6152896 30262932 · DOI
  87. Hewitt N.; Rauk A. Mechanism of Hydrogen Peroxide Production by Copper-Bound Amyloid Beta Peptide: A Theoretical Study. J. Phys. Chem. B 2009, 113 (4), 1202– 1209. 10.1021/jp807327a. 19123835 · DOI
  88. Kong X.; Zhao Z.; Lei X.; Zhang B.; Dai D.; Jiang L. Interaction of Metal Ions with the His13-His14 Sequence Relevant to Alzheimers Disease. J. Phys. Chem. A 2015, 119 (14), 3528– 3534. 10.1021/acs.jpca.5b01443. 25801452 · DOI
  89. Arrigoni F.; Di Carlo C.; Rovetta A.; De Gioia L.; Zampella G.; Bertini L. Superoxide Reduction by Cu-Amyloid Beta Peptide Complexes: A Density Functional Theory Study. Eur. J. Inorg. Chem. 2022, 2022 ((21),). 10.1002/ejic.202200245. · DOI
  90. Raffa D. F.; Rauk A. Molecular Dynamics Study of the Beta Amyloid Peptide of Alzheimer's Disease and Its Divalent Copper Complexes. No. Figure 2007, 111, 3789– 3799. 10.1021/jp0689621. 17388547 · DOI
  91. Furlan S.; Hureau C.; Faller P.; La Penna G. Modeling the Cu+ Binding in the 1–16 Region of the Amyloid-β Peptide Involved in Alzheimer’s Disease. J. Phys. Chem. B 2010, 114 (46), 15119– 15133. 10.1021/jp102928h. 21038888 · DOI
  92. Alí-Torres J.; Maréchal J. D.; Rodríguez-Santiago L.; Sodupe M. Three Dimensional Models of Cu 2+-Aβ(1–16) Complexes from Computational Approaches. J. Am. Chem. Soc. 2011, 133 (38), 15008– 15014. 10.1021/ja203407v. 21846101 · DOI
  93. Alí-Torres J.; Mirats A.; Maréchal J. D.; Rodríguez-Santiago L.; Sodupe M. Modeling Cu2+-Aβ Complexes from Computational Approaches. AIP Adv. 2015, 5 (9), 0– 11. 10.1063/1.4921072. · DOI
  94. Reybier K.; Ayala S.; Alies B.; Rodrigues J. V.; Bustos Rodriguez S.; La Penna G.; Collin F.; Gomes C. M.; Hureau C.; Faller P. Free Superoxide Is an Intermediate in the Production of H 2 O 2 by Copper(I)-Aβ Peptide and O 2. Angew. Chem. 2016, 128 (3), 1097– 1101. 10.1002/ange.201508597. 26629876 · DOI
  95. Rao R.; Georgieff M. K. Iron in Fetal and Neonatal Nutrition. Semin. Fetal Neonatal Med. 2007, 12 (1), 54– 63. 10.1016/j.siny.2006.10.007. 17157088 PMC2048487 · DOI
  96. Christy A. L.; Manjrekar P. A.; Babu R. P.; Hegde A.; Rukmini M. S. Influence of Iron Deficiency Anemia on Hemoglobin A1C Levels in Diabetic Individuals with Controlled Plasma Glucose Levels. Iran. Biomed. J. 2014, 18 (2), 88– 92. 10.6091/ibj.1257.2014. 24518549 PMC3933917 · DOI
  97. Levi S.; Finazzi D. Neurodegeneration with Brain Iron Accumulation: Update on Pathogenic Mechanisms. Front. Pharmacol. 2014, 5 (May), 1– 21. 10.3389/fphar.2014.00099. 24847269 PMC4019866 · DOI · Paper page
  98. Wang X.; Zhang J.; Zhou L.; Xu B.; Ren X.; He K.; Nie L.; Li X.; Liu J.; Yang X.; Yuan J. Long-Term Iron Exposure Causes Widespread Molecular Alterations Associated with Memory Impairment in Mice. Food Chem. Toxicol. 2019, 130 (March), 242– 252. 10.1016/j.fct.2019.05.038. 31136779 · DOI
  99. Schrag M.; Mueller C.; Oyoyo U.; Smith M. A.; Kirsch W. M. Iron, Zinc and Copper in the Alzheimer’s Disease Brain: A Quantitative Meta-Analysis. Some Insight on the Influence of Citation Bias on Scientific Opinion. Prog. Neurobiol. 2011, 94 (3), 296– 306. 10.1016/j.pneurobio.2011.05.001. 21600264 PMC3134620 · DOI
  100. Akatsu H.; Hori A.; Yamamoto T.; Yoshida M.; Mimuro M.; Hashizume Y.; Tooyama I.; Yezdimer E. M. Transition Metal Abnormalities in Progressive Dementias. BioMetals 2012, 25 (2), 337– 350. 10.1007/s10534-011-9504-8. 22080191 · DOI
  101. Wong B. X.; Tsatsanis A.; Lim L. Q.; Adlard P. A.; Bush A. I.; Duce J. A. Β-Amyloid Precursor Protein Does Not Possess Ferroxidase Activity But Does Stabilize the Cell Surface Ferrous Iron Exporter Ferroportin. PLoS One 2014, 9 (12), 1– 19. 10.1371/journal.pone.0114174. PMC4252103 25464026 · DOI
  102. Kemna E. H. J. M.; Tjalsma H.; Willems H. L.; Swinkels D. W. Hepcidin: From Discovery to Differential Diagnosis. Haematologica 2008, 93 (1), 90– 97. 10.3324/haematol.11705. 18166790 · DOI
  103. Raha A. A.; Vaishnav R. A.; Friedland R. P.; Bomford A.; Raha-Chowdhury R. The Systemic Iron-Regulatory Proteins Hepcidin and Ferroportin Are Reduced in the Brain in Alzheimer’s Disease. Acta Neuropathol. Commun. 2013, 1 (1), 1– 19. 10.1186/2051-5960-1-55. PMC3893417 24252754 · DOI
  104. Banerjee P.; Sahoo A.; Anand S.; Ganguly A.; Righi G.; Bovicelli P.; Saso L.; Chakrabarti S. Multiple Mechanisms of Iron-Induced Amyloid Beta-Peptide Accumulation in SHSY5Y Cells: Protective Action of Negletein. NeuroMolecular Med. 2014, 16 (4), 787– 798. 10.1007/s12017-014-8328-4. 25249289 · DOI
  105. Silvestri L.; Camaschella C. A Potential Pathogenetic Role of Iron in Alzheimer’s Disease. J. Cell. Mol. Med. 2008, 12 (5A), 1548– 1550. 10.1111/j.1582-4934.2008.00356.x. 18466351 PMC3918070 · DOI
  106. Liu B.; Moloney A.; Meehan S.; Morris K.; Thomas S. E.; Serpell L. C.; Hider R.; Marciniak S. J.; Lomas D. A.; Crowther D. C. Iron Promotes the Toxicity of Amyloid β Peptide by Impeding Its Ordered Aggregation. J. Biol. Chem. 2011, 286 (6), 4248– 4256. 10.1074/jbc.M110.158980. 21147772 PMC3039358 · DOI
  107. Alí-Torres J.; Rodríguez-Santiago L.; Sodupe M.; Rauk A. Structures and Stabilities of Fe2+/3+ Complexes Relevant to Alzheimer’s Disease: An Ab Initio Study. J. Phys. Chem. A 2011, 115 (45), 12523– 12530. 10.1021/jp2026626. 21678945 · DOI
  108. Orjuela A. L.; Núñez-Zarur F.; Alí-Torres J. A Computational Protocol for the Calculation of the Standard Reduction Potential of Iron Complexes: Application to Fe 2+/3+ -Aβ Model Systems Relevant to Alzheimer’s Disease. RSC Adv. 2022, 12 (37), 24077– 24087. 10.1039/D2RA03907A. 36200023 PMC9451132 · DOI
  109. Rajendran R.; Minqin R.; Ynsa M. D.; Casadesus G.; Smith M. A.; Perry G.; Halliwell B.; Watt F. A Novel Approach to the Identification and Quantitative Elemental Analysis of Amyloid Deposits-Insights into the Pathology of Alzheimer’s Disease. Biochem. Biophys. Res. Commun. 2009, 382 (1), 91– 95. 10.1016/j.bbrc.2009.02.136. 19258010 · DOI
  110. Guo C.; Wang P.; Zhong M. L.; Wang T.; Huang X. S.; Li J. Y.; Wang Z. Y. Deferoxamine Inhibits Iron Induced Hippocampal Tau Phosphorylation in the Alzheimer Transgenic Mouse Brain. Neurochem. Int. 2013, 62 (2), 165– 172. 10.1016/j.neuint.2012.12.005. 23262393 · DOI
  111. Gumpelmayer M.; Nguyen M.; Molnár G.; Bousseksou A.; Meunier B.; Robert A. Magnetite Fe3O4 Has No Intrinsic Peroxidase Activity, and Is Probably Not Involved in Alzheimer’s Oxidative Stress. Angew. Chemie - Int. Ed. 2018, 57 (45), 14758– 14763. 10.1002/anie.201807676. 30230674 · DOI
  112. Kepp K. P. Bioinorganic Chemistry of Alzheimer’s Disease. Chem. Rev. 2012, 112 (10), 5193– 5239. 10.1021/cr300009x. 22793492 · DOI
  113. Miura T.; Suzuki K.; Takeuchi H. Binding of Iron(III) to the Single Tyrosine Residue of Amyloid β-Peptide Probed by Raman Spectroscopy. J. Mol. Struct. 2001, 598 (1), 79– 84. 10.1016/S0022-2860(01)00807-9. · DOI
  114. Exley C.; Mold M. J. The Binding, Transport and Fate of Aluminium in Biological Cells. J. Trace Elem. Med. Biol. 2015, 30, 90– 95. 10.1016/j.jtemb.2014.11.002. 25498314 · DOI
  115. Klatzo I.; Wisniewski H.; Streicher E. Experimental Production of Neurofibrillary Degeneration. J. Neuropathol Exp Neurol 1965, 24, 198– 199. 10.1097/00005072-196504000-00002. 14280496 · DOI
  116. Schreeder M. T.; Favero M. S.; Hughes J. R.; Petersen N. J.; Bennett P. H.; Maynard J. E. Dialysis Encephalopathy and Aluminum Exposure: An Epidemiologic Analysis. J. Chronic Dis. 1983, 36 (8), 581– 593. 10.1016/0021-9681(83)90146-7. 6885959 · DOI
  117. Mcdermott J. R.; Smith A. I.; Iqbal K.; Wisniewski H. M. Brain Aluminum in Aging and Alzheimer Disease. Neurology 1979, 29 (6), 809– 814. 10.1212/WNL.29.6.809. 572003 · DOI
  118. Reusche E.; Koch V.; Lindner B.; Harrison A. P.; Friedrich H. J. Alzheimer Morphology Is Not Increased in Dialysis-Associated Encephalopathy and Long-Term Hemodialysis. Acta Neuropathol 2001, 101 (3), 211– 216. 10.1007/s004010000253. 11307619 · DOI
  119. Munoz D. G. Is Exposure to Aluminum a Risk Factor for the Development of Alzheimer Disease? - No. Arch. Neurol. 1998, 55 (5), 737– 739. 10.1001/archneur.55.5.737. 9605734 · DOI
  120. Fukuzumi S.; Ohtsu H.; Ohkubo K.; Itoh S.; Imahori H. Formation of Superoxide-Metal Ion Complexes and the Electron Transfer Catalysis. Coord. Chem. Rev. 2002, 226 (1–2), 71– 80. 10.1016/S0010-8545(01)00435-0. · DOI
  121. Mujika J. I.; Rodríguez-Guerra Pedregal J.; Lopez X.; Ugalde J. M.; Rodríguez-Santiago L.; Sodupe M.; Maréchal J. D. Elucidating the 3D Structures of Al(III)-Aβ Complexes: A Template Free Strategy Based on the Pre-Organization Hypothesis. Chem. Sci. 2017, 8 (7), 5041– 5049. 10.1039/C7SC01296A. 28970891 PMC5613242 · DOI
  122. Ruipérez F.; Mujika J. I.; Ugalde J. M.; Exley C.; Lopez X. Pro-Oxidant Activity of Aluminum: Promoting the Fenton Reaction by Reducing Fe(III) to Fe(II). J. Inorg. Biochem. 2012, 117, 118– 123. 10.1016/j.jinorgbio.2012.09.008. 23085591 · DOI
  123. Ayton S.; Lei P.; Bush A. I. Metallostasis in Alzheimer’s Disease. Free Radic. Biol. Med. 2013, 62, 76– 89. 10.1016/j.freeradbiomed.2012.10.558. 23142767 · DOI
  124. Bortolato M.; Chen K.; Shih J. C. Monoamine Oxidase Inactivation: From Pathophysiology to Therapeutics. Adv. Drug Delivery Rev. 2008, 60 (13–14), 1527– 1533. 10.1016/j.addr.2008.06.002. PMC2630537 18652859 · DOI · Paper page
  125. Zhang H. Y. One-Compound-Multiple-Targets Strategy to Combat Alzheimer’s Disease. FEBS Lett. 2005, 579 (24), 5260– 5264. 10.1016/j.febslet.2005.09.006. 16194540 · DOI
  126. Sampietro A.; Pérez-Areales F. J.; Martínez P.; Arce E. M.; Galdeano C.; Muñoz-Torrero D. Unveiling the Multitarget Anti-Alzheimer Drug Discovery Landscape: A Bibliometric Analysis. Pharmaceuticals 2022, 15 (5), 1– 23. 10.3390/ph15050545. PMC9146451 35631371 · DOI
  127. Fan J.; De Lannoy I. A. M. Pharmacokinetics. Biochem. Pharmacol. 2014, 87 (1), 93– 120. 10.1016/j.bcp.2013.09.007. 24055064 · DOI · Paper page
  128. Pardridge W. M. Alzheimer’s Disease Drug Development and the Problem of the Blood-Brain Barrier. Alzheimer's Dement. 2009, 5 (5), 427– 432. 10.1016/j.jalz.2009.06.003. 19751922 PMC2756824 · DOI
  129. Lipinski C. A.; Lombardo F.; Dominy B. W.; Feeney P. J. Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings. Adv. Drug Delivery Rev. 1997, 23, 3– 25. 10.1016/S0169-409X(96)00423-1. 11259830 · DOI
  130. Rodríguez-Rodríguez C.; Rimola A.; Alí-Torres J.; Sodupe M.; González-Duarte P. In Silico Strategies for the Selection of Chelating Compounds with Potential Application in Metal-Promoted Neurodegenerative Diseases. J. Comput. Aided. Mol. Des. 2011, 25 (1), 21– 30. 10.1007/s10822-010-9396-7. 21061044 · DOI
  131. Clark D. E. Rapid Calculation of Polar Molecular Surface Area and Its Application to the Prediction of Transport Phenomena. 2. Prediction of Blood–Brain Barrier Penetration. J. Pharm. Sci. 1999, 88 (8), 815– 821. 10.1021/js980402t. 10430548 · DOI
  132. Storr T. Multifunctional Compounds for the Treatment of Alzheimer’s Disease. Can. J. Chem. 2021, 99 (1), 1– 9. 10.1139/cjc-2020-0279. · DOI
  133. Santos M. A.; Chand K.; Chaves S. Recent Progress in Multifunctional Metal Chelators as Potential Drugs for Alzheimer’s Disease. Coord. Chem. Rev. 2016, 327–328, 287– 303. 10.1016/j.ccr.2016.04.013. · DOI
  134. Bolognesi M. L.; Bartolini M.; Tarozzi A.; Morroni F.; Lizzi F.; Milelli A.; Minarini A.; Rosini M.; Hrelia P.; Andrisano V.; Melchiorre C. Multitargeted Drugs Discovery: Balancing Anti-Amyloid and Anticholinesterase Capacity in a Single Chemical Entity. Bioorg. Med. Chem. Lett. 2011, 21 (9), 2655– 2658. 10.1016/j.bmcl.2010.12.093. 21236667 · DOI
  135. Rosini M.; Simoni E.; Bartolini M.; Tarozzi A.; Matera R.; Milelli A.; Hrelia P.; Andrisano V.; Bolognesi M. L.; Melchiorre C. Exploiting the Lipoic Acid Structure in the Search for Novel Multitarget Ligands against Alzheimer’s Disease. Eur. J. Med. Chem. 2011, 46 (11), 5435– 5442. 10.1016/j.ejmech.2011.09.001. 21924801 · DOI
  136. Cavalli A.; Bolognesi M. L.; Capsoni S.; Andrisano V.; Bartolini M.; Margotti E.; Cattaneo A.; Recanatini M.; Melchiorre C. A Small Molecule Targeting the Multifactorial Nature of Alzheimer’s Disease. Angew. Chemie - Int. Ed. 2007, 46 (20), 3689– 3692. 10.1002/anie.200700256. 17397121 · DOI
  137. Rimola A.; Alí-Torres J.; Rodríguez-Rodríguez C.; Poater J.; Matito E.; Solà M.; Sodupe M. Ab Initio Design of Chelating Ligands Relevant to Alzheimer’s Disease: Influence of Metalloaromaticity. J. Phys. Chem. A 2011, 115 (45), 12659– 12666. 10.1021/jp203465h. 21699142 · DOI
  138. Gyurcsik B.; Nagy L. Carbohydrates as Ligands: Coordination Equilibria and Structure of the Metal Complexes. Coord. Chem. Rev. 2000, 203 (1), 81– 149. 10.1016/S0010-8545(99)00183-6. · DOI
  139. Segal M.; Zlokovic B. V. The Blood-Brain Barrier, Amino Acids and Peptides; Springer, 2011.
  140. Selvaraj C.; Chandra I.; Singh S. K. Artificial Intelligence and Machine Learning Approaches for Drug Design: Challenges and Opportunities for the Pharmaceutical Industries. Mol. Divers. 2022, 26 (3), 1893– 1913. 10.1007/s11030-021-10326-z. 34686947 PMC8536481 · DOI
  141. Drew S. C. The Case for Abandoning Therapeutic Chelation of Copper Ions in Alzheimer’s Disease. Front. Neurosci. 2017, 11 ((JUN),). 10.3389/fnins.2017.00317. PMC5455140 28626387 · DOI
  142. Squitti R.; Salustri C.; Rongioletti M.; Siotto M. Commentary: The Case for Abandoning Therapeutic Chelation of Copper Ions in Alzheimer’s Disease. Front. Neurol. 2017, 8 (SEP), 10– 13. 10.3389/fneur.2017.00503. 28993754 PMC5622302 · DOI
  143. Bush A. I.; Tanzi R. E. Therapeutics for Alzheimer’s Disease Based on the Metal Hypothesis. Neurotherapeutics 2008, 5 (3), 421– 432. 10.1016/j.nurt.2008.05.001. 18625454 PMC2518205 · DOI
  144. Caballero A. B.; Iranzo O.; Hautier A.; Sabaté R.; Gamez P. Peptidic Scaffolds to Reduce the Interaction of Cu(II) Ions with β-Amyloid Protein. Inorg. Chem. 2020, 59 (1), 837– 846. 10.1021/acs.inorgchem.9b03099. 31855423 · DOI
  145. Ferrada E.; Arancibia V.; Loeb B.; Norambuena E.; Olea-Azar C.; Huidobro-Toro J. P. Stoichiometry and Conditional Stability Constants of Cu(II) or Zn(II) Clioquinol Complexes; Implications for Alzheimer’s and Huntington’s Disease Therapy. Neurotoxicology 2007, 28 (3), 445– 449. 10.1016/j.neuro.2007.02.004. 17382398 · DOI
  146. Kung H. F.; Lee C. W.; Zhuang Z. P.; Kung M. P.; Hou C.; Plössl K. Novel Stilbenes as Probes for Amyloid Plaques. J. Am. Chem. Soc. 2001, 123 (50), 12740– 12741. 10.1021/ja0167147. 11741464 · DOI
  147. Priyadarsini K. I.; Maity D. K.; Naik G. H.; Kumar M. S.; Unnikrishnan M. K.; Satav J. G.; Mohan H. Role of Phenolic O-H and Methylene Hydrogen on the Free Radical Reactions and Antioxidant Activity of Curcumin. Free Radic. Biol. Med. 2003, 35 (5), 475– 484. 10.1016/S0891-5849(03)00325-3. 12927597 · DOI
  148. Wanninger S.; Lorenz V.; Subhan A.; Edelmann F. T. Metal Complexes of Curcumin - Synthetic Strategies, Structures and Medicinal Applications. Chem. Soc. Rev. 2015, 44 (15), 4986– 5002. 10.1039/C5CS00088B. 25964104 · DOI
  149. Patil P.; Thakur A.; Sharma A.; Flora S. J. S. Natural Products and Their Derivatives as Multifunctional Ligands against Alzheimer’s Disease. Drug Dev. Res. 2020, 81 (2), 165– 183. 10.1002/ddr.21587. 31820476 · DOI
  150. Chaparro D.; Flores-Gaspar A.; Alí-Torres J. Computational Design of Copper Ligands with Controlled Metal Chelating, Pharmacokinetics, and Redox Properties for Alzheimer’s Disease. J. Alzheimer's Dis. 2021, 82 (s1), 1– 15. 10.3233/JAD-200911. 34032611 · DOI
  151. Chaparro D.; Alí-Torres J. Assessment of the Isodesmic Method in the Calculation of Standard Reduction Potential of Copper Complexes. J. Mol. Model. 2017, 23 ((10),). 10.1007/s00894-017-3469-7. 28936691 · DOI
  152. Clarke E. T.; Martell A. E. Stabilities of 1,2-Dimethyl-3-Hydroxy-4-Pyridinone Chelates of Divalent and Trivalent Metal Ions. Inorg. Chim. Acta 1992, 191 (1), 57– 63. 10.1016/S0020-1693(00)80327-8. · DOI · Paper page
  153. Hershko C.; Konijn A. M.; Link G. Iron Chelators for Thalassaemia. Br. J. Hamaetol. 1998, 101 (3), 399– 406. 10.1046/j.1365-2141.1998.00726.x. 9633877 · DOI
  154. Hider R. C.; Bittel D.; Andrews G. K. Competition between Iron(III)-Selective Chelators and Zinc-Finger Domains for Zinc(II). Biochem. Pharmacol. 1999, 57 (9), 1031– 1035. 10.1016/S0006-2952(99)00014-3. 10796073 · DOI
  155. Cohen A. R.; Galanello R.; Piga A.; De Sanctis V.; Tricta F. Safety and Effectiveness of Long-Term Therapy with the Oral Iron Chelator Deferiprone. Blood 2003, 102 (5), 1583– 1587. 10.1182/blood-2002-10-3280. 12763939 · DOI
  156. Galanello R. Deferiprone in the Treatment of Transfusion-Dependent Thalassemia: A Review and Perspective. Ther. Clin. Risk Manag. 2007, 3 (5), 795– 805. 18473004 PMC2376085
  157. Nurchi V. M.; Crisponi G.; Pivetta T.; Donatoni M.; Remelli M. Potentiometric, Spectrophotometric and Calorimetric Study on Iron(III) and Copper(II) Complexes with 1,2-Dimethyl-3-Hydroxy-4-Pyridinone. J. Inorg. Biochem. 2008, 102 (4), 684– 692. 10.1016/j.jinorgbio.2007.10.012. 18061272 · DOI
  158. Velasco-Sánchez D.; Aracil A.; Montero R.; Mas A.; Jiménez L.; O’Callaghan M.; Tondo M.; Capdevila A.; Blanch J.; Artuch R.; Pineda M. Combined Therapy with Idebenone and Deferiprone in Patients with Friedreich’s Ataxia. Cerebellum 2011, 10 (1), 1– 8. 10.1007/s12311-010-0212-7. 20865357 · DOI
  159. Prasanthi J. R. P.; Schrag M.; Dasari B.; Marwarha G.; Dickson A.; Kirsch W. M.; Ghribi O. Deferiprone Reduces Amyloid-β and Tau Phosphorylation Levels but Not Reactive Oxygen Species Generation in Hippocampus of Rabbits Fed a Cholesterol-Enriched Diet. J. Alzheimer's Dis. 2012, 30 (1), 167– 182. 10.3233/JAD-2012-111346. 22406440 PMC3645354 · DOI
  160. Asmari M.; Michalcová L.; Alhazmi H. A.; Glatz Z.; El Deeb S. Investigation of Deferiprone Binding to Different Essential Metal Ions Using Microscale Thermophoresis and Electrospray Ionization Mass Spectrometry. Microchem. J. 2018, 137, 98– 104. 10.1016/j.microc.2017.10.004. · DOI
  161. Ayton S.; Woodward M.; Ellis K. A.; Lim Y. Y.; Maruff P. T.; Desmond P. M.; Salvado O.; Fazlollahi A.; Rowe C. C.; Churilov L.; Bush A. I. Deferiprone to Delay Dementia (the 3D Trial). Alzheimer's Dement. 2020, 16 (S9), 44107 10.1002/alz.044107. · DOI
  162. Kaviani S.; Izadyar M.; Housaindokht M. R. A DFT Study on the Metal Ion Selectivity of Deferiprone Complexes. Comput. Biol. Chem. 2020, 86 (March), 107267 10.1016/j.compbiolchem.2020.107267. 32470911 · DOI
  163. Bortolami M.; Pandolfi F.; De Vita D.; Carafa C.; Messore A.; Di Santo R.; Feroci M.; Costi R.; Chiarotto I.; Bagetta D.; Alcaro S.; Colone M.; Stringaro A.; Scipione L. New Deferiprone Derivatives as Multi-Functional Cholinesterase Inhibitors: Design, Synthesis and in Vitro Evaluation. Eur. J. Med. Chem. 2020, 198, 1– 17. 10.1016/j.ejmech.2020.112350. 32380385 · DOI
  164. Grossi C.; Francese S.; Casini A.; Rosi M. C.; Luccarini I.; Fiorentini A.; Gabbiani C.; Messori L.; Moneti G.; Casamenti F. Clioquinol Decreases Amyloid-β Burden and Reduces Working Memory Impairment in a Transgenic Mouse Model of Alzheimer’s Disease. J. Alzheimer's Dis. 2009, 17 (2), 423– 440. 10.3233/JAD-2009-1063. 19363260 · DOI
  165. Treiber C.; Simons A.; Strauss M.; Hafner M.; Cappai R.; Bayer T. A.; Multhaup G. Clioquinol Mediates Copper Uptake and Counteracts Copper Efflux Activities of the Amyloid Precursor Protein of Alzheimer’s Disease. J. Biol. Chem. 2004, 279 (50), 51958– 51964. 10.1074/jbc.M407410200. 15465814 · DOI
  166. Meade T. W. Subacute Myelo Optic Neuropathy and Clioquinol. An Epidemiological Case History for Diagnosis. J. Epidemiol. Community Health 1975, 29 (3), 157– 169. 10.1136/jech.29.3.157. PMC478909 127638 · DOI
  167. Mao X.; Schimmer A. D. The Toxicology of Clioquinol. Toxicol. Lett. 2008, 182 (1–3), 1– 6. 10.1016/j.toxlet.2008.08.015. 18812216 · DOI
  168. Rodríguez-Santiago L.; Alí-Torres J.; Vidossich P.; Sodupe M. Coordination Properties of a Metal Chelator Clioquinol to Zn2+ Studied by Static DFT and Ab Initio Molecular Dynamics. Phys. Chem. Chem. Phys. 2015, 17 (20), 13582– 13589. 10.1039/C5CP01615K. 25939963 · DOI
  169. Silva T. U.; de Paula Machado S. Electronic Study of Reactivity of the Substituted 8-Hydroxyquinoline to the Bind Site of the β-Amyloid Peptide to Zinc Ion. Quim. Nova 2019, 42 (8), 885– 890. 10.21577/0100-4042.20170411. · DOI
  170. Adlard P. A.; Cherny R. A.; Finkelstein D. I.; Gautier E.; Robb E.; Cortes M.; Volitakis I.; Liu X.; Smith J. P.; Perez K.; Laughton K.; Li Q. X.; Charman S. A.; Nicolazzo J. A.; Wilkins S.; Deleva K.; Lynch T.; Kok G.; Ritchie C. W.; Tanzi R. E.; Cappai R.; Masters C. L.; Barnham K. J.; Bush A. I. Rapid Restoration of Cognition in Alzheimer’s Transgenic Mice with 8-Hydroxy Quinoline Analogs Is Associated with Decreased Interstitial Aβ. Neuron 2008, 59 (1), 43– 55. 10.1016/j.neuron.2008.06.018. 18614028 · DOI · Paper page
  171. Lannfelt L.; Blennow K.; Zetterberg H.; Batsman S.; Ames D.; Harrison J.; Masters C. L.; Targum S.; Bush A. I.; Murdoch R.; Wilson J.; Ritchie C. W. Safety, Efficacy, and Biomarker Findings of PBT2 in Targeting Aβ as a Modifying Therapy for Alzheimer’s Disease: A Phase IIa, Double-Blind, Randomised, Placebo-Controlled Trial. Lancet Neurol 2008, 7 (9), 779– 786. 10.1016/S1474-4422(08)70167-4. 18672400 · DOI · Paper page
  172. Faux N. G.; Ritchie C. W.; Gunn A.; Rembach A.; Tsatsanis A.; Bedo J.; Harrison J.; Lannfelt L.; Blennow K.; Zetterberg H.; Ingelsson M.; Masters C. L.; Tanzi R. E.; Cummings J. L.; Herd C. M.; Bush A. I. PBT2 Rapidly Improves Cognition in Alzheimer’s Disease: Additional Phase II Analyses. J. Alzheimer's Dis. 2010, 20 (2), 509– 516. 10.3233/JAD-2010-1390. 20164561 · DOI
  173. Oliveri V.; Vecchio G. 8-Hydroxyquinolines in Medicinal Chemistry: A Structural Perspective. Eur. J. Med. Chem. 2016, 120, 252– 274. 10.1016/j.ejmech.2016.05.007. 27191619 · DOI
  174. Summers K. L.; Roseman G. P.; Sopasis G. J.; Millhauser G. L.; Harris H. H.; Pickering I. J.; George G. N. Copper(II) Binding to PBT2 Differs from That of Other 8-Hydroxyquinoline Chelators: Implications for the Treatment of Neurodegenerative Protein Misfolding Diseases. Inorg. Chem. 2020, 59 (23), 17519– 17534. 10.1021/acs.inorgchem.0c02754. 33226796 PMC7927943 · DOI
  175. Ryan T. M.; Roberts B. R.; McColl G.; Hare D. J.; Doble P. A.; Li Q. X.; Lind M.; Roberts A. M.; Mertens H. D. T.; Kirby N.; Pham C. L. L.; Hinds M. G.; Adlard P. A.; Barnham K. J.; Curtain C. C.; Masters C. L. Stabilization of Nontoxic Ajβ-Oligomers: Insights into the Mechanism of Action of Hydroxyquinolines in Alzheimer’s Disease. J. Neurosci. 2015, 35 (7), 2871– 2884. 10.1523/JNEUROSCI.2912-14.2015. 25698727 PMC6605585 · DOI
  176. De Freitas L. V.; Da Silva C. C. P.; Ellena J.; Costa L. A. S.; Rey N. A. Structural and Vibrational Study of 8-Hydroxyquinoline-2-Carboxaldehyde Isonicotinoyl Hydrazone - A Potential Metal-Protein Attenuating Compound (MPAC) for the Treatment of Alzheimer’s Disease. Spectrochim. Acta - Part A Mol. Biomol. Spectrosc. 2013, 116, 41– 48. 10.1016/j.saa.2013.06.105. 23896296 · DOI
  177. Hauser-Davis R. A.; De Freitas L. V.; Cukierman D. S.; Cruz W. S.; Miotto M. C.; Landeira-Fernandez J.; Valiente-Gabioud A. A.; Fernández C. O.; Rey N. A. Disruption of Zinc and Copper Interactions with Aβ(1–40) by a Non-Toxic, Isoniazid-Derived, Hydrazone: A Novel Biometal Homeostasis Restoring Agent in Alzheimer’s Disease Therapy?. Metallomics 2015, 7 (5), 743– 747. 10.1039/C5MT00003C. 25860559 · DOI
  178. Cukierman D. S.; Pinheiro A. B.; Castiñeiras-Filho S. L. P.; da Silva A. S. P.; Miotto M. C.; De Falco A.; de P Ribeiro T.; Maisonette S.; da Cunha A. L. M. C.; Hauser-Davis R. A.; Landeira-Fernandez J.; Aucélio R. Q.; Outeiro T. F.; Pereira M. D.; Fernández C. O.; Rey N. A. A Moderate Metal-Binding Hydrazone Meets the Criteria for a Bioinorganic Approach towards Parkinson’s Disease: Therapeutic Potential, Blood-Brain Barrier Crossing Evaluation and Preliminary Toxicological Studies. J. Inorg. Biochem. 2017, 170, 160– 168. 10.1016/j.jinorgbio.2017.02.020. 28249224 · DOI
  179. De Falco A.; Kincheski G. C.; Atrián-Blasco E.; Hureau C.; Ferreira S. T.; Rey N. A. The Aroylhydrazone INHHQ Prevents Memory Impairment Induced by Alzheimer’s-Linked Amyloid-β Oligomers in Mice. Behav. Pharmacol. 2020, 31 (8), 738– 747. 10.1097/FBP.0000000000000578. 32773452 · DOI
  180. Yang X.; Cai P.; Liu Q.; Wu J.; Yin Y.; Wang X.; Kong L. Novel 8-Hydroxyquinoline Derivatives Targeting β-Amyloid Aggregation, Metal Chelation and Oxidative Stress against Alzheimer’s Disease. Bioorg. Med. Chem. 2018, 26 (12), 3191– 3201. 10.1016/j.bmc.2018.04.043. 29729985 · DOI
  181. Lee S.; Zheng X.; Krishnamoorthy J.; Savelieff M. G.; Park H. M.; Brender J. R.; Kim J. H.; Derrick J. S.; Kochi A.; Lee H. J.; Kim C.; Ramamoorthy A.; Bowers M. T.; Lim M. H. Rational Design of a Structural Framework with Potential Use to Develop Chemical Reagents That Target and Modulate Multiple Facets of Alzheimer’s Disease. J. Am. Chem. Soc. 2014, 136 (1), 299– 310. 10.1021/ja409801p. 24397771 PMC4096303 · DOI
  182. Vajragupta O.; Boonchoong P.; Watanabe H.; Tohda M.; Kummasud N.; Sumanont Y. Manganese Complexes of Curcumin and Its Derivatives: Evaluation for the Radical Scavenging Ability and Neuroprotective Activity. Free Radic. Biol. Med. 2003, 35 (12), 1632– 1644. 10.1016/j.freeradbiomed.2003.09.011. 14680686 · DOI
  183. Sumanont Y.; Murakami Y.; Tohda M.; Vajragupta O.; Watanabe H.; Matsumoto K. Effects of Manganese Complexes of Curcumin and Diacetylcurcumin on Kainic Acid-Induced Neurotoxic Responses in the Rat Hippocampus. Biol. Pharm. Bull. 2007, 30 (9), 1732– 1739. 10.1248/bpb.30.1732. 17827730 · DOI
  184. Belda R.; Blasco S.; Verdejo B.; Jiménez H. R.; Doménech-Carbó A.; Soriano C.; Latorre J.; Terencio C.; García-España E. Homo- and Heterobinuclear Cu2+ and Zn2+ Complexes of Abiotic Cyclic Hexaazapyridinocyclophanes as SOD Mimics. Dalt. Trans. 2013, 42 (31), 11194– 11204. 10.1039/c3dt51012c. 23807542 · DOI
  185. Lim G. P.; Chu T.; Yang F.; Beech W.; Frautschy S. A.; Cole G. M. The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse. J. Neurosci. 2001, 21 (21), 8370– 8377. 10.1523/JNEUROSCI.21-21-08370.2001. 11606625 PMC6762797 · DOI · Paper page
  186. Tang M.; Taghibiglou C.; Liu J. The Mechanisms of Action of Curcumin in Alzheimer’s Disease. J. Alzheimer's Dis. 2017, 58 (4), 1003– 1016. 10.3233/JAD-170188. 28527218 · DOI
  187. Lakey-Beitia J.; González Y.; Doens D.; Stephens D. E.; Santamaría R.; Murillo E.; Gutiérrez M.; Fernández P. L.; Rao K. S.; Larionov O. V.; Durant-Archibold A. A. Assessment of Novel Curcumin Derivatives as Potent Inhibitors of Inflammation and Amyloid-β Aggregation in Alzheimer’s Disease. J. Alzheimer's Dis. 2017, 60 (s1), S59– S68. 10.3233/JAD-170071. 28453488 PMC5737775 · DOI
  188. Orjuela A.; Lakey-Beitia J.; Mojica-Flores R.; Hegde M. L.; Lans I.; Alí-Torres J.; Rao K. S. S. Computational Evaluation of Interaction between Curcumin Derivatives and Amyloid-β Monomers and Fibrils: Relevance to Alzheimer’s Disease. J. Alzheimer's Dis. 2021, 82 (s1), S321– S333. 10.3233/JAD-200941. 33337368 PMC8206224 · DOI
  189. Zhao X. Z.; Jiang T.; Wang L.; Yang H.; Zhang S.; Zhou P. Interaction of Curcumin with Zn(II) and Cu(II) Ions Based on Experiment and Theoretical Calculation. J. Mol. Struct. 2010, 984 (1–3), 316– 325. 10.1016/j.molstruc.2010.09.049. · DOI
  190. Pradhan K.; Das G.; Kar C.; Mukherjee N.; Khan J.; Mahata T.; Barman S.; Ghosh S. Rhodamine-Based Metal Chelator: A Potent Inhibitor of Metal-Catalyzed Amyloid Toxicity. ACS Omega 2020, 5 (30), 18958– 18967. 10.1021/acsomega.0c02235. 32775897 PMC7408195 · DOI
  191. Yang X.; Qiang X.; Li Y.; Luo L.; Xu R.; Zheng Y.; Cao Z.; Tan Z.; Deng Y. Pyridoxine-Resveratrol Hybrids Mannich Base Derivatives as Novel Dual Inhibitors of AChE and MAO-B with Antioxidant and Metal-Chelating Properties for the Treatment of Alzheimer’s Disease. Bioorg. Chem. 2017, 71, 305– 314. 10.1016/j.bioorg.2017.02.016. 28267984 · DOI
  192. Iraji A.; Firuzi O.; Khoshneviszadeh M.; Tavakkoli M.; Mahdavi M.; Nadri H.; Edraki N.; Miri R. Multifunctional Iminochromene-2H-Carboxamide Derivatives Containing Different Aminomethylene Triazole with BACE1 Inhibitory, Neuroprotective and Metal Chelating Properties Targeting Alzheimer’s Disease. Eur. J. Med. Chem. 2017, 141, 690– 702. 10.1016/j.ejmech.2017.09.057. 29107423 · DOI
  193. Kochi A.; Eckroat T. J.; Green K. D.; Mayhoub A. S.; Lim M. H.; Garneau-Tsodikova S. A Novel Hybrid of 6-Chlorotacrine and Metal–Amyloid-β Modulator for Inhibition of Acetylcholinesterase and Metal-Induced Amyloid-β Aggregation. Chem. Sci. 2013, 4 (11), 4137– 4145. 10.1039/c3sc51902c. · DOI
  194. Hiremathad A.; Keri R. S.; Esteves A. R.; Cardoso S. M.; Chaves S.; Santos M. A. Novel Tacrine-Hydroxyphenylbenzimidazole Hybrids as Potential Multitarget Drug Candidates for Alzheimer’s Disease. Eur. J. Med. Chem. 2018, 148, 255– 267. 10.1016/j.ejmech.2018.02.023. 29466775 · DOI
  195. Chaves S.; Hiremathad A.; Tomas D.; Keri R. S.; Piemontese L.; Santos M. A. Exploring the Chelating Capacity of 2-Hydroxyphenyl-Benzimidazole Based Hybrids with Multi-Target Ability as Anti-Alzheimer’s Agents. New J. Chem. 2018, 42 (20), 16503– 16515. 10.1039/C8NJ00117K. · DOI
  196. Silva T.; Mohamed T.; Shakeri A.; Rao P. P. N.; Soares da Silva P.; Remião F.; Borges F. Repurposing Nitrocatechols: 5-Nitro-α-Cyanocarboxamide Derivatives of Caffeic Acid and Caffeic Acid Phenethyl Ester Effectively Inhibit Aggregation of Tau-Derived Hexapeptide AcPHF6. Eur. J. Med. Chem. 2019, 167, 146– 152. 10.1016/j.ejmech.2019.02.006. 30771602 · DOI

Cited by

Sorted by citations

Authors
Puentes-Díaz, N., Chaparro, D., Morales-Morales, D., Flores-Gaspar, A., & Alí-Torres, J.
Affiliations
  • Departamento de Química, Universidad Nacional de Colombia−Sede Bogotá, Bogotá 11301, Colombia
  • Universidad Nacional de Colombia (CO)
  • Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Ciudad de México 04510, México
  • Departamento de Química, Universidad Militar Nueva Granada, Cajicá 250240, Colombia
ORCID
Venue
ACS Omega
Publisher
American Chemical Society (ACS)
Published
2023-01-25
Volume
8
Issue
5
Pages
4508-4526
ISSN
2470-1343 (ISSN-L)
DOI
10.1021/acsomega.2c06939
PMC
PMC9909689
OpenAlex
W4319056900
Cited by
67
References
24
Citations by year
2026: 13 · 2025: 24 · 2024: 22 · 2023: 8
FWCI
2.25
Type
journal article
Language
en
Open access
Licence
Locations
  • ACS Omega (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Universidad Nacional de Colombia
  • Universidad Militar Nueva Granada (INV-CIAS-3408)
  • Center of Excellence in Scientific Computing (CoE-SciCo)
  • Divisi??n de Investigaci??n Sede Bogot??
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Aluminum toxicity and tolerance in plants and animals
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
Alzheimer's disease, copper, iron, aluminum, metal cations, reactive oxygen species, oxidative stress, multifunctional ligands, transition metal coordination, neuroprotection, metal chelators

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