Recent Development of Bifunctional Small Molecules to Study Metal‐Amyloid‐β Species in Alzheimer′s Disease
Open accessAbstract
Alzheimer's disease (AD) is a multifactorial neurodegenerative disease related to the deposition of aggregated amyloid-β (Aβ) peptides in the brain. It has been proposed that metal ion dyshomeostasis and miscompartmentalization contribute to AD progression, especially as metal ions (e.g., Cu(II) and Zn(II)) found in Aβ plaques of the diseased brain can bind to Aβ and be linked to aggregation and neurotoxicity. The role of metal ions in AD pathogenesis, however, is uncertain. To accelerate understanding in this area and contribute to therapeutic development, recent efforts to devise suitable chemical reagents that can target metal ions associated with Aβ have been made using rational structure-based design that combines two functions (metal chelation and Aβ interaction) in the same molecule. This paper presents bifunctional compounds developed by two different design strategies (linkage or incorporation) and discusses progress in their applications as chemical tools and/or potential therapeutics.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Metal chelators reduce metal-mediated Aβ aggregation, ROS formation, and neurotoxicity in vitro.
“metal chelators have been shown to reduce metal-mediated Aβ aggregation, ROS formation, and neurotoxicity in vitro.23−26”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [24]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139 · see citing works
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484 · cited 1× · see citing works
“SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 623051, 9 pages doi:10.4061/2011/623051”
MethodInfluentialSoluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · cited 1× · see citing works
“Current evidence suggests that monomers and fibrils are relatively benign, while soluble oligomers, including dimers, are responsible for the neurotoxicity leading to dementia [8, 9].”
BackgroundImaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496 · cited 2× · see citing works
“This radiolabeled iodinated ligand can be a useful SPECT reagent over some current PET probes for a number of reasons including practicality of administering the compound as well as cost and availability of SPECT equipment in clinical settings [64–66].”
BackgroundShankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685 · cited 1× · see citing works
“Current evidence suggests that monomers and fibrils are relatively benign, while soluble oligomers, including dimers, are responsible for the neurotoxicity leading to dementia [8, 9].”
BackgroundLeVine, H. (1993) · Protein Science · doi:10.1002/pro.5560020312 · Cited by 2,268 · see citing works
Copper, iron and zinc in Alzheimer's disease senile plaques
Lovell, M. A., Robertson, J. D., Teesdale, W. J., Campbell, J. L., & Markesbery, W. R. (1998) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(98)00092-6 · Cited by 2,120 · cited 2× · see citing works
“Elevated concentrations of Cu(II) and Zn(II) have been observed in senile plaques [1, 4, 13–15, 24, 25]; in particular, high concentrations of labile zinc are found in the regions of the brain most affected by AD, the cortex and hippocampus [4, 13–17, 19].”
BackgroundGaggelli, E., Kozlowski, H., Valensin, D., & Valensin, G. (2006) · Chemical Reviews · doi:10.1021/cr040410w · Cited by 1,729 · see citing works
Amyloid-β–induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks
Palop, J. J., & Mucke, L. (2010) · Nature Neuroscience · doi:10.1038/nn.2583 · Cited by 1,651 · cited 1× · see citing works
“SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 623051, 9 pages doi:10.4061/2011/623051”
MethodInfluentialCherny, R. A., Atwood, C. S., Xilinas, M. E., Gray, D. N., Jones, W. D., McLean, C. A., Barnham, K. J., Volitakis, I., Fraser, F. W., Kim, Y.-S., et al. (2001) · Neuron · doi:10.1016/s0896-6273(01)00317-8 · Cited by 1,447 · cited 1× · see citing works
“SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 623051, 9 pages doi:10.4061/2011/623051”
MethodInfluentialCurcumin has potent anti‐amyloidogenic effects for Alzheimer's β‐amyloid fibrils in vitro
Ono, K., Hasegawa, K., Naiki, H., & Yamada, M. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20025 · Cited by 1,254 · see citing works
Alzheimer's disease: strategies for disease modification
Citron, M. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd2896 · Cited by 1,060 · cited 1× · see citing works
“Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is a growing worldwide health concern among aging populations [1, 2].”
BackgroundThe Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide
Soscia, S. J., Kirby, J. E., Washicosky, K. J., Tucker, S. M., Ingelsson, M., Hyman, B., Burton, M. A., Goldstein, L. E., Duong, S., Tanzi, R. E., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009505 · Cited by 1,060 · cited 1× · see citing works
“SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 623051, 9 pages doi:10.4061/2011/623051”
MethodInfluentialRitchie, C. W., Bush, A. I., Mackinnon, A., Macfarlane, S., Mastwyk, M., MacGregor, L., Kiers, L., Cherny, R., Li, Q.-X., Tammer, A., et al. (2003) · Archives of Neurology · doi:10.1001/archneur.60.12.1685 · Cited by 988 · cited 1× · see citing works
“SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 623051, 9 pages doi:10.4061/2011/623051”
MethodInfluentialArrest of -Amyloid Fibril Formation by a Pentapeptide Ligand
Tjernberg, L. O., Näslund, J., Lindqvist, F., Johansson, J., Karlström, A. R., Thyberg, J., Terenius, L., & Nordstedt, C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8545 · Cited by 963 · see citing works
Soto, C. A., Sigurdsson, E. M., Morelli, L., Kumar, R., Castaño, E. M., & Frangione, B. (1998) · Nature Medicine · doi:10.1038/nm0798-822 · Cited by 874 · see citing works
Lannfelt, L., Blennow, K., Zetterberg, H., Batsman, S., Ames, D., Harrison, J., Masters, C. L., Targum, S., Bush, A. I., Murdoch, R., et al. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70167-4 · Cited by 725 · cited 1× · see citing works
“SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 623051, 9 pages doi:10.4061/2011/623051”
MethodInfluentialMetals in Alzheimer's and Parkinson's Diseases
Barnham, K. J., & Bush, A. I. (2008) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2008.02.019 · Cited by 695 · cited 4× · see citing works
“Elevated concentrations of Cu(II) and Zn(II) have been observed in senile plaques [1, 4, 13–15, 24, 25]; in particular, high concentrations of labile zinc are found in the regions of the brain most affected by AD, the cortex and hippocampus [4, 13–17, 19].”
BackgroundInfluentialAdlard, P. A., Cherny, R. A., Finkelstein, D. I., Gautier, E., Robb, E., Cortes, M., Volitakis, I., Liu, X., Smith, J. P., Perez, K., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.018 · Cited by 672 · cited 1× · see citing works
“SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 623051, 9 pages doi:10.4061/2011/623051”
MethodInfluentialAlzheimer's Disease: From Pathology to Therapeutic Approaches
Jakob‐Roetne, R., & Jacobsen, H. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200802808 · Cited by 626 · cited 2× · see citing works
“Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is a growing worldwide health concern among aging populations [1, 2].”
BackgroundMiller, L. M., Wang, Q., Telivala, T. P., Smith, R., Lanzirotti, A., & Judith Miklossy, A. (2005) · Journal of Structural Biology · doi:10.1016/j.jsb.2005.09.004 · Cited by 588 · cited 3× · see citing works
“participate in AD pathogenesis is still unclear [1, 3, 4, 13– 25].”
BackgroundComputational methods for the prediction of ‘drug-likeness’
Clark, D. E., & Pickett, S. D. (2000) · Drug Discovery Today · doi:10.1016/s1359-6446(99)01451-8 · Cited by 583 · cited 5× · see citing works
“Additionally, the structure fulfills the criteria of the restrictive terms of Lipinski’s rules and the logBB values, indicating that it may be drug-like and BBB permeable [48, 49].”
BackgroundMethodInfluentialTherapeutics for Alzheimer's Disease Based on the Metal Hypothesis
Bush, A. I., & Tanzi, R. E. (2008) · Neurotherapeutics · doi:10.1016/j.nurt.2008.05.001 · Cited by 566 · see citing works
Bioinorganic chemistry of copper and zinc ions coordinated to amyloid-β peptide
Faller, P., & Hureau, C. (2009) · Dalton Trans. · doi:10.1039/b813398k · Cited by 530 · see citing works
Klunk, W. E., Wang, Y., Huang, G.-F., Debnath, M. L., Holt, D. P., & Mathis, C. A. (2001) · Life Sciences · doi:10.1016/s0024-3205(01)01232-2 · Cited by 457 · cited 4× · see citing works
“It has been proposed that ThT could be a useful framework to pursue in the development of Aβ imaging agents [47].”
BackgroundInfluentialThe chemistry of Alzheimer’s disease
Rauk, A. (2009) · Chemical Society Reviews · doi:10.1039/b807980n · Cited by 417 · cited 4× · see citing works
“Based on the close proximity of these residues to the metal chelation site (H6, H13, and H14) [3, 4, 18, 21, 22], 1 could possibly interact with metal ions in that portion of the peptide.”
BackgroundInfluentialAlzheimer's disease, metal ions and metal homeostatic therapy
Zatta, P., Drago, D., Bolognin, S., & Sensi, S. L. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.05.002 · Cited by 369 · cited 1× · see citing works
“It has been suggested that Al(III) can cause a change in the Aβ conformation that stabilizes the oligomeric state and increases surface hydrophobicity, which may cause an increase in toxicity and membrane permeability [16, 19, 26].”
BackgroundFluorescent stains, with special reference to amyloid and connective tissues.
Ps, V., & Cf, C. (1959) · PubMed · Cited by 363 · see citing works
Naturally occurring phytochemicals for the prevention of Alzheimer’s disease
Kim, J., Lee, H. J., & Lee, K. W. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06562.x · Cited by 354 · cited 1× · see citing works
“Curcumin (Figure 2) has shown antiamyloidogenic, antioxidative, and anti-inflammatory properties [59–61].”
BackgroundMetals and amyloid‐β in Alzheimer's disease
Maynard, C. J., Bush, A. I., Masters, C. L., Cappai, R., & Li, Q. (2005) · International Journal of Experimental Pathology · doi:10.1111/j.0959-9673.2005.00434.x · Cited by 353 · cited 5× · see citing works
“Metal ion dyshomeostasis and miscompartmentalization also are thought to play a significant part in the progression of AD [1, 3, 4, 13–23].”
BackgroundInfluentialCauses of oxidative stress in Alzheimer disease
Zhu, X., Su, B., Wang, X., Smith, M. A., & Perry, G. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7218-4 · Cited by 336 · cited 3× · see citing works
“Metal ion dyshomeostasis and miscompartmentalization also are thought to play a significant part in the progression of AD [1, 3, 4, 13–23].”
BackgroundScott, L. E., & Orvig, C. (2009) · Chemical Reviews · doi:10.1021/cr9000176 · Cited by 332 · cited 5× · see citing works
“Based on the close proximity of these residues to the metal chelation site (H6, H13, and H14) [3, 4, 18, 21, 22], 1 could possibly interact with metal ions in that portion of the peptide.”
BackgroundInfluentialReinke, A. A., & Gestwicki, J. E. (2007) · Chemical Biology & Drug Design · doi:10.1111/j.1747-0285.2007.00557.x · Cited by 330 · cited 1× · see citing works
“The structure-activity relationships of Aβ aggregation inhibitors based on curcumin have been studied, and three necessary structural features were identified: the presence of two terminal aromatic groups, the substitution of these aromatics, and the length and flexibility of the linker between the aromatic groups [62…”
BackgroundFaller, P. (2009) · ChemBioChem · doi:10.1002/cbic.200900321 · Cited by 285 · cited 4× · see citing works
“Based on the close proximity of these residues to the metal chelation site (H6, H13, and H14) [3, 4, 18, 21, 22], 1 could possibly interact with metal ions in that portion of the peptide.”
BackgroundInfluentialBiological metals and Alzheimer's disease: Implications for therapeutics and diagnostics
Duce, J. A., & Bush, A. I. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.04.003 · Cited by 281 · cited 2× · see citing works
“It has been suggested that Al(III) can cause a change in the Aβ conformation that stabilizes the oligomeric state and increases surface hydrophobicity, which may cause an increase in toxicity and membrane permeability [16, 19, 26].”
BackgroundChoi, J.-S., Braymer, J. J., Nanga, R. P. R., Ramamoorthy, A., & Lim, M. H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006091107 · Cited by 264 · see citing works
Self-citationHureau, C., & Faller, P. (2009) · Biochimie · doi:10.1016/j.biochi.2009.03.013 · Cited by 259 · see citing works
A Strategy for Designing Inhibitors of β-Amyloid Toxicity
Ghanta, J., Shen, C.-L., Kiessling, L. L., & Murphy, R. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.47.29525 · Cited by 224 · cited 1× · see citing works
““β-sheet blockers” that interfere with amyloidogenesis by interacting with the portions of the peptide responsible for facilitating self-aggregation have been investigated [52–56].”
BackgroundMetal Chelation as a Potential Therapy for Alzheimer's Disease
Cuajungco, M. P., Faget, K. Y., Huang, X., Tanzi, R. E., & Bush, A. I. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06938.x · Cited by 215 · cited 1× · see citing works
“Based on this hypothesis, disruption of metal-Aβ interactions via metal chelation therapy has been proposed in order to reduce neurotoxicity of metal-Aβ species and restore metal ion homeostasis in the brain [1, 3, 4, 13, 15–17, 19, 27–35].”
BackgroundRodríguez-Rodríguez, C., Sánchez de Groot, N., Rimola, A., Álvarez-Larena, Á., Lloveras, V., Vidal-Gancedo, J., Ventura, S., Vendrell, J., Sodupe, M., & González-Duarte, P. (2009) · Journal of the American Chemical Society · doi:10.1021/ja806062g · Cited by 210 · see citing works
Recognition Sequence Design for Peptidyl Modulators of β-Amyloid Aggregation and Toxicity
Pallitto, M. M., Ghanta, J., Heinzelman, P., Kiessling, L. L., & Murphy, R. M. (1999) · Biochemistry · doi:10.1021/bi982119e · Cited by 208 · see citing works
Metals ions and neurodegeneration
Molina‐Holgado, F., Hider, R. C., Gaeta, A., Williams, R., & Francis, P. T. (2007) · BioMetals · doi:10.1007/s10534-006-9033-z · Cited by 207 · cited 5× · see citing works
“Metal ion dyshomeostasis and miscompartmentalization also are thought to play a significant part in the progression of AD [1, 3, 4, 13–23].”
BackgroundInfluentialSmall Molecule Modulators of Copper-Induced Aβ Aggregation
Hindo, S. S., Mancino, A. M., Braymer, J. J., Liu, Y., Vivekanandan, S., Ramamoorthy, A., & Lim, M. H. (2009) · Journal of the American Chemical Society · doi:10.1021/ja907045h · Cited by 203 · cited 5× · see citing works
“One bifunctional IMPY derivative, 1, has been reported by Lim and coworkers (Figure 5(b)) [42].”
BackgroundInfluentialSelf-citationKung, H. F., Choi, S., Qü, W., Zhang, W., & Skovronsky, D. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm901039z · Cited by 200 · see citing works
Ryu, E. K., Choe, Y. S., Lee, K.-H., Choi, Y., & Kim, B. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm0607193 · Cited by 198 · see citing works
IMPY: an improved thioflavin-T derivative for in vivo labeling of β-amyloid plaques
Kung, M., Hou, C., Zhuang, Z., Zhang, B., Skovronsky, D., Trojanowski, J. Q., Lee, V. M. ‐., & Kung, H. F. (2002) · Brain Research · doi:10.1016/s0006-8993(02)03436-4 · Cited by 196 · cited 1× · see citing works
“The need for in vivo Aβ plaque imaging molecules also has led to the development of a ThT analogue, IMPY (Figure 2) [63–68].”
BackgroundLee, J., Friedman, J. E., Angel, I., Kozak, A., & Koh, J. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.01.005 · Cited by 190 · cited 1× · see citing works
“Based on this hypothesis, disruption of metal-Aβ interactions via metal chelation therapy has been proposed in order to reduce neurotoxicity of metal-Aβ species and restore metal ion homeostasis in the brain [1, 3, 4, 13, 15–17, 19, 27–35].”
BackgroundLee, H., Casadesús, G., Zhu, X., Takeda, A., Perry, G. L., & Smith, M. A. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1297.001 · Cited by 180 · cited 1× · see citing works
“SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 623051, 9 pages doi:10.4061/2011/623051”
MethodInfluentialNovel Stilbenes as Probes for Amyloid Plaques
Kung, H. F., Lee, C., Zhuang, Z., Kung, M., Hou, C., & Plöessl, K. (2001) · Journal of the American Chemical Society · doi:10.1021/ja0167147 · Cited by 179 · see citing works
Verdile, G. (2004) · Pharmacological Research · doi:10.1016/j.phrs.2003.12.028 · Cited by 177 · cited 1× · see citing works
“SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 623051, 9 pages doi:10.4061/2011/623051”
MethodInfluentialMinding metals: Tailoring multifunctional chelating agents for neurodegenerative disease
Perez, L. R., & Franz, K. J. (2010) · Dalton Trans. · doi:10.1039/b919237a · Cited by 156 · cited 1× · see citing works
“Utilizing Approach II, three categories of compounds have been reported: (a) the ThT-based molecules, HBX, HBT, BM, and their iodinated derivatives (HBX = 2-(2-hydroxyphenyl) benzoxazole; HBT = 2-(2-hydroxyphenyl)benzothiazole; BM = 2-(2-aminophenyl)benzimidazole), (b) the IMPY derivative (1) (1 = 2-[4-(dimethylamino)…”
BackgroundF-18 Stilbenes as PET Imaging Agents for Detecting β-Amyloid Plaques in the Brain
Zhang, W., Oya, S., Kung, M., Hou, C., Maier, D. L., & Kung, H. F. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm050166g · Cited by 151 · see citing works
Newberg, A. B., Wintering, N., Plößl, K., Hochold, J., Stabin, M. G., Watson, M., Skovronsky, D., Clark, C. M., Kung, M., & Kung, H. F. (2006) · PubMed · Cited by 143 · see citing works
Preliminary studies of a novel bifunctional metal chelator targeting Alzheimer's amyloidogenesis
Dedeoglu, A., Cormier, K., Payton, S., Tseitlin, K. A., Kremsky, J. N., Lai, L., Li, X., Moir, R. D., Tanzi, R. E., Bush, A. I., et al. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.08.016 · Cited by 141 · cited 1× · see citing works
“were the first to report a neutral ThTconjugated EDTA derivative, XH1 (Figure 4), for metalassociated Aβ species [39].”
BackgroundKung, M., Hou, C., Zhuang, Z., Skovronsky, D., & Kung, H. F. (2004) · Brain Research · doi:10.1016/j.brainres.2004.08.004 · Cited by 134 · see citing works
Aluminum-triggered structural modifications and aggregation of β-amyloids
Ricchelli, F., Drago, D., Filippi, B., Tognon, G., & Zatta, P. F. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5141-0 · Cited by 128 · cited 1× · see citing works
“It has been suggested that Al(III) can cause a change in the Aβ conformation that stabilizes the oligomeric state and increases surface hydrophobicity, which may cause an increase in toxicity and membrane permeability [16, 19, 26].”
BackgroundSequestration of Copper from β-Amyloid Promotes Selective Lysis by Cyclen-Hybrid Cleavage Agents
Wu, W., Lei, P., Liu, Q. R., Hu, J., Gunn, A. P., Chen, M., Rui, Y., Su, X., Xie, Z., Zhao, Y., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804722200 · Cited by 124 · cited 4× · see citing works
“Cyc-KLVFF (Figure 4) was effective toward reducing metal-triggered Aβ aggregation and neurotoxicity including Cu(II)-induced ROS production in vitro and in neuronal cell culture [40].”
BackgroundMethodInfluentialPoduslo, J. F., Curran, G. L., Kumar, A. R., Frangione, B., & Soto, C. A. (1999) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(19990605)39:3 · Cited by 114 · see citing works
Chen, T., Wang, X., He, Y., Zhang, C., Wu, Z., Liao, K., Wang, J., & Guo, Z. (2009) · Inorganic Chemistry · doi:10.1021/ic900025x · Cited by 110 · see citing works
Chelation therapy for neurodegenerative diseases
Bolognin, S., Drago, D., Luigi Messori, A., & Zatta, P. F. (2009) · Medicinal Research Reviews · doi:10.1002/med.20148 · Cited by 97 · cited 1× · see citing works
“Based on this hypothesis, disruption of metal-Aβ interactions via metal chelation therapy has been proposed in order to reduce neurotoxicity of metal-Aβ species and restore metal ion homeostasis in the brain [1, 3, 4, 13, 15–17, 19, 27–35].”
BackgroundRodríguez‐Rodríguez, C., Rimola, A., Rodrı́guez-Santiago, L., Ugliengo, P., Álvarez‐Larena, Á., Gutiérrez‐de‐Terán, H., Sodupe, M., & Gonzalez-Duarte, P. (2010) · Chemical Communications · doi:10.1039/b912396b · Cited by 91 · see citing works
Clioquinol-Zinc Chelate: A Candidate Causative Agent of Subacute Myelo-Optic Neuropathy
Arbiser, J. L., Kraeft, S.-K., van Leeuwen, R., Hurwitz, S. J., Selig, M., Dickersin, G. R., Flint, A., Byers, H. R., & Chen, L. B. (1998) · Molecular Medicine · doi:10.1007/bf03401927 · Cited by 85 · see citing works
Crouch, P., White, A., & Bush, A. I. (2007) · The FEBS Journal · doi:10.1111/j.1742-4658.2007.05918.x · Cited by 81 · cited 1× · see citing works
“Based on this hypothesis, disruption of metal-Aβ interactions via metal chelation therapy has been proposed in order to reduce neurotoxicity of metal-Aβ species and restore metal ion homeostasis in the brain [1, 3, 4, 13, 15–17, 19, 27–35].”
BackgroundKung, M., Hou, C., Zhuang, Z., Cross, A. J., Maier, D. L., & Kung, H. (2004) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-004-1487-z · Cited by 72 · cited 3× · see citing works
“IMPY also has shown favorable pharmacokinetic properties in the Tg2576 and PS1/APP transgenic mouse models as well as safety in human patients [64–66].”
BackgroundLeuma Yona, R., Mazères, S., Faller, P., & Gras, E. (2008) · ChemMedChem · doi:10.1002/cmdc.200700188 · Cited by 72 · see citing works
Metal complexes as artificial proteases: toward catalytic drugs
Suh, J., & Chei, W. S. (2008) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2008.01.028 · Cited by 70 · cited 1× · see citing works
“Cyclen is a macrocyclic metal chelator that can modulate Aβ aggregation and neurotoxicity in vitro and in cortical neuronal cells of C57BL6/J mice, and it has been shown that cyclen-Co(III) complexes have proteolytic activity [57, 58].”
BackgroundUpdate on amyloid imaging: From healthy aging to Alzheimer’s disease
Wolk, D. A., & Klunk, W. E. (2009) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-009-0051-4 · Cited by 62 · cited 2× · see citing works
“This radiolabeled iodinated ligand can be a useful SPECT reagent over some current PET probes for a number of reasons including practicality of administering the compound as well as cost and availability of SPECT equipment in clinical settings [64–66].”
BackgroundTwo Functions, One Molecule: A Metal‐Binding and a Targeting Moiety to Combat Alzheimer's Disease
Hureau, C., Sasaki, I., Gras, E., & Faller, P. (2010) · ChemBioChem · doi:10.1002/cbic.201000102 · Cited by 49 · cited 1× · see citing works
“Utilizing Approach II, three categories of compounds have been reported: (a) the ThT-based molecules, HBX, HBT, BM, and their iodinated derivatives (HBX = 2-(2-hydroxyphenyl) benzoxazole; HBT = 2-(2-hydroxyphenyl)benzothiazole; BM = 2-(2-aminophenyl)benzimidazole), (b) the IMPY derivative (1) (1 = 2-[4-(dimethylamino)…”
BackgroundCai, L., Cuevas, J., Temme, J. S., Herman, M. M., Dagostin, C., Widdowson, D. A., Innis, R. B., & Pike, V. W. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm0702231 · Cited by 43 · see citing works
Characterization of Radioiodinated Ligand Binding to Amyloid β Plaques
Kung, M., Zhuang, Z., Hou, C., Jin, L., & Kung, H. F. (2003) · Journal of Molecular Neuroscience · doi:10.1385/jmn:20:3:249 · Cited by 15 · cited 1× · see citing works
“The need for in vivo Aβ plaque imaging molecules also has led to the development of a ThT analogue, IMPY (Figure 2) [63–68].”
BackgroundUnproved Modality in the Treatment of Alzheimer‐Type Dementia
Cardelli, M. B., Russell, M., Bagne, C. A., & Pomara, N. (1985) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1985.tb04620.x · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [48]Lipinski CA Lombardo F Dominy BW Feeney PJ Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings Advanced Drug Delivery Reviews 2001 46 1–3 3 26 11259830
Cited by
Sorted by citations
Bioinorganic Chemistry of Alzheimer’s Disease
Kepp, K. P. (2012) · Chemical Reviews · doi:10.1021/cr300009x · Cited by 672 · see citing works
Biological metals and metal-targeting compounds in major neurodegenerative diseases
Barnham, K. J., & Bush, A. I. (2014) · Chem. Soc. Rev. · doi:10.1039/c4cs00138a · Cited by 497 · see citing works
Misfolded proteins in Alzheimer's disease and type II diabetes
DeToma, A. S., Salamekh, S., Ramamoorthy, A., & Lim, M. H. (2011) · Chemical Society Reviews · doi:10.1039/c1cs15112f · Cited by 359 · see citing works
Self-citationChoi, J.-S., Braymer, J. J., Nanga, R. P. R., Ramamoorthy, A., & Lim, M. H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006091107 · Cited by 264 · see citing works
“Shao H, Jao S, Ma K, Zagorski MG (1999) Solution structures of micelle-bound amyloid β-(1-40) and β-(1-42) peptides of Alzheimer’s disease.”
BackgroundMethodInfluentialSelf-citationMetal-associated amyloid-β species in Alzheimer's disease
Pithadia, A. S., & Lim, M. H. (2012) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2012.01.016 · Cited by 259 · see citing works
Self-citationHyung, S., DeToma, A. S., Brender, J., Lee, S., Vivekanandan, S., Kochi, A., Choi, J.-S., Ramamoorthy, A., Ruotolo, B. T., & Lim, M. H. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220326110 · Cited by 238 · see citing works
“structure of amyloid-beta(1-40) in an aqueous environment.”
Self-citationBifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ<sub>42</sub>Peptide
Sharma, A. K., Pavlova, S. T., Kim, J., Finkelstein, D., Hawco, N. J., Rath, N. P., Kim, J., & Mirica, L. M. (2012) · Journal of the American Chemical Society · doi:10.1021/ja210588m · Cited by 202 · see citing works
Singh, S. K., Srivastav, S., Yadav, A. K., Srikrishna, S., & Perry, G. L. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/7361613 · Cited by 188 · see citing works
Lee, S., Zheng, X., Krishnamoorthy, J., Savelieff, M. G., Park, H. M., Brender, J., Kim, J. H., Derrick, J. S., Kochi, A., Lee, H. J., et al. (2013) · Journal of the American Chemical Society · doi:10.1021/ja409801p · Cited by 185 · see citing works
Self-citationSavelieff, M. G., DeToma, A. S., Derrick, J. S., & Lim, M. H. (2014) · Accounts of Chemical Research · doi:10.1021/ar500152x · Cited by 174 · see citing works
Self-citationRodríguez-Rodríguez, C., Telpoukhovskaia, M., & Orvig, C. (2012) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2012.03.008 · Cited by 151 · see citing works
Li, S., Wang, X., & Kong, L. (2013) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2013.10.068 · Cited by 110 · see citing works
Myricetin: A Naturally Occurring Regulator of Metal‐Induced Amyloid‐β Aggregation and Neurotoxicity
DeToma, A. S., Choi, J., Braymer, J. J., & Lim, M. H. (2011) · ChemBioChem · doi:10.1002/cbic.201000790 · Cited by 99 · see citing works
Self-citationBraymer, J. J., Choi, J.-S., DeToma, A. S., Wang, C., Nam, K., Kampf, J. W., Ramamoorthy, A., & Lim, M. H. (2011) · Inorganic Chemistry · doi:10.1021/ic2012205 · Cited by 88 · see citing works
Self-citationLan, J., Ding, Y., Liu, Y., Kang, P., Hou, J., Zhang, X., Xie, S., & Zhang, T. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.07.055 · Cited by 76 · see citing works
Lincoln, K. M., Gonzalez, P., Richardson, T. E., Julovich, D. A., Saunders, R. E., Simpkins, J. W., & Green, K. N. (2013) · Chemical Communications · doi:10.1039/c2cc36808k · Cited by 67 · see citing works
Redox-Active Metal Ions and Amyloid-Degrading Enzymes in Alzheimer’s Disease
Kim, N., & Lee, H. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147697 · Cited by 67 · see citing works
An N-Heterocyclic Amine Chelate Capable of Antioxidant Capacity and Amyloid Disaggregation
Lincoln, K. M., Richardson, T. E., Rutter, L., Gonzalez, P., Simpkins, J. W., & Green, K. N. (2012) · ACS Chemical Neuroscience · doi:10.1021/cn300060v · Cited by 59 · see citing works
Sharma, A. K., Schultz, J. W., Prior, J. T., Rath, N. P., & Mirica, L. M. (2017) · Inorganic Chemistry · doi:10.1021/acs.inorgchem.7b01883 · Cited by 60 · see citing works
DeToma, A. S., Krishnamoorthy, J., Nam, Y., Lee, H. J., Brender, J., Kochi, A., Lee, D., Onnis, V., Congiu, C., Manfredini, S., et al. (2014) · Chemical Science · doi:10.1039/c4sc01531b · Cited by 58 · see citing works
Self-citationCopper Chelators: Chemical Properties and Bio-medical Applications
Tegoni, M., Valensin, D., Toso, L., & Remelli, M. (2014) · Current Medicinal Chemistry · doi:10.2174/0929867321666140601161939 · Cited by 56 · see citing works
Clawing back: broadening the notion of metal chelators in medicine
Franz, K. J. (2013) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2012.12.021 · Cited by 50 · see citing works
Lan, J., Zhang, T., Liu, Y., Yang, J., Xie, S., Liu, J., Miao, Z.-Y., & Ding, Y. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.02.045 · Cited by 50 · see citing works
Sharma, A. K., Kim, J., Prior, J. T., Hawco, N. J., Rath, N. P., Kim, J., & Mirica, L. M. (2014) · Inorganic Chemistry · doi:10.1021/ic500926c · Cited by 48 · see citing works
Sun, L., Sharma, A. K., Han, B.-H., & Mirica, L. M. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00376 · Cited by 45 · see citing works
Balakrishnan, M., Layek, S., Balaji, S., Trivedi, V., & Iyer, P. K. (2015) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00205 · Cited by 42 · see citing works
Synthesis and characterization of IMPY derivatives that regulate metal-induced amyloid-β aggregation
Choi, J.-S., Braymer, J. J., Park, S. K., Mustafa, S., Chae, J., & Lim, M. H. (2011) · Metallomics · doi:10.1039/c0mt00077a · Cited by 41 · see citing works
Self-citationBaul, T. S. B., Kundu, S., Linden, A., Raviprakash, N., Manna, S. K., & da Silva, M. F. C. G. (2013) · Dalton Transactions · doi:10.1039/c3dt52062e · Cited by 40 · see citing works
Azo-dyes based small bifunctional molecules for metal chelation and controlling amyloid formation
Rana, M., Cho, H., Roy, T. K., Mirica, L. M., & Sharma, A. K. (2017) · Inorganica Chimica Acta · doi:10.1016/j.ica.2017.11.029 · Cited by 40 · see citing works
Inhibition of Cu‐Amyloid‐β by using Bifunctional Peptides with β‐Sheet Breaker and Chelator Moieties
Jensen, M., Canning, A., Chiha, S., Bouquerel, P., Pedersen, J. T., Østergaard, J., Cuvillier, O., Sasaki, I., Hureau, C., & Faller, P. (2012) · Chemistry - A European Journal · doi:10.1002/chem.201103546 · Cited by 37 · see citing works
Liu, L., Chen, Y., Zeng, R., Liu, Y., Xie, S., Lan, J., Ding, Y., Yang, Y., Yang, J., & Zhang, T. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.104685 · Cited by 36 · see citing works
Exploring the reactivity of flavonoid compounds with metal-associated amyloid-β species
He, X., Park, H. M., Hyung, S., DeToma, A. S., Kim, C., Ruotolo, B. T., & Lim, M. H. (2012) · Dalton Transactions · doi:10.1039/c2dt12207c · Cited by 31 · see citing works
Self-citationBrazilin inhibits the Zn2+-mediated aggregation of amyloid β-protein and alleviates cytotoxicity
Guo, J., Sun, W., & Liu, F. (2017) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2017.09.015 · Cited by 29 · see citing works
Froestl, W., Pfeifer, A., & Muhs, A. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-121729 · Cited by 27 · see citing works
Gonzalez, P., da Costa, V. C. P., Hyde, K., Wu, Q., Annunziata, O., Rizo, J., Akkaraju, G. R., & Green, K. N. (2014) · Metallomics · doi:10.1039/c4mt00161c · Cited by 29 · see citing works
Eslami, M., Nezafat, N., Negahdaripour, M., & Ghasemi, Y. (2019) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2018.1564701 · Cited by 27 · see citing works
Wang, Z., Xie, S., Li, X., Wu, J., Wang, X., & Kong, L. (2015) · RSC Advances · doi:10.1039/c5ra13594j · Cited by 23 · see citing works
Yu, M., Ryan, T. M., Ellis, S., Bush, A. I., Triccas, J. A., Rutledge, P. J., & Todd, M. H. (2014) · Metallomics · doi:10.1039/c4mt00122b · Cited by 20 · see citing works
Márquez, M., Blancas‐Mejía, L. M., Campos, A., Rojas-Ochoa, L. F., Castañeda‐Hernández, G., & Quintanar, L. (2014) · Metallomics · doi:10.1039/c4mt00257a · Cited by 20 · see citing works
Braymer, J. J., Merrill, N. M., & Lim, M. H. (2011) · Inorganica Chimica Acta · doi:10.1016/j.ica.2011.08.056 · Cited by 16 · see citing works
Self-citationKim, M., & Lim, M. H. (2021) · Bulletin of the Korean Chemical Society · doi:10.1002/bkcs.12372 · Cited by 14 · see citing works
Self-citationBaul, T. S. B., Kundu, S., Singh, P., Shaveta, S., & da Silva, M. F. C. G. (2014) · Dalton Transactions · doi:10.1039/c4dt03151b · Cited by 13 · see citing works
Xu, L., Gao, K., Bao, C., & Wang, X. (2012) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-012-9588-4 · Cited by 11 · see citing works
Lan, J., Zhang, T., Liu, Y., Zhang, Y., Hou, J., Xie, S., Yang, J. L., Ding, Y., & Cai, Z. (2017) · MedChemComm · doi:10.1039/c6md00586a · Cited by 9 · see citing works
Wang, L., Zhang, Y., Yu, X., He, H., & Zhang, J. (2012) · Synthetic Metals · doi:10.1016/j.synthmet.2012.09.012 · Cited by 7 · see citing works
Design and Applications of Bifunctional Small Molecules in Biology
Boyd, S. R., Chang, L., de Rezende, W. C., Raji, I. O., Kandel, P., Holmes, S. L., & Young, D. W. (2020) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2020.140534 · Cited by 7 · see citing works
Green, K. N., Johnston, H. M., Burnett, M. E., & Brewer, S. M. (2016) · Comments on Inorganic Chemistry · doi:10.1080/02603594.2016.1241616 · Cited by 3 · see citing works
Eslami, M., Hashemianzadeh, S. M., Moghaddam, K. G., Khorsandi, L., & Sajadi, S. A. S. (2015) · RSC Advances · doi:10.1039/c5ra11346f · Cited by 3 · see citing works
Tosonyan, S. A. A. (2018) · OPUS - Open Publications of UTS Scholars (University of Technology Sydney)
Conte‐Daban, A. (2017) · theses.fr (ABES) · doi:10.70675/77c5d103zebd9z49dcza4fcz7c76f7c64d1b
“But CSF assay could be less reliable because Aβ levels can fluctuate.(29) The Aβ accumulation biomarkers used in PET imaging can also be used in the CSF assay.”
- Authors
- Braymer, J. J., DeToma, A. S., Choi, J.-S., Ko, K. S., & Lim, M. H.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Lim, Mi Hee
- Venue
- International Journal of Alzheimer’s Disease
- Publisher
- Wiley
- Published
- 2010-12-08
- Volume
- 2011
- Issue
- 1
- Pages
- 623051-623051
- ISSN
- 2090-0252 (ISSN-L)
- 2090-8024
- PMC
- PMC3004374
- OpenAlex
- W2052046119
- Cited by
- 50
- References
- 72
- Citations by year
- 2021: 3 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 7 · 2016: 1 · 2015: 4 · 2014: 9 · 2013: 7 · 2012: 9
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- International Journal of Alzheimer s Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion, cc-by)
- Funders
- Horace H. Rackham School of Graduate Studies from the University of Michigan (NIRG-10-172326, NRF-2009-352-F00042)
- Alzheimer's Art Quilt Initiative (NIRG-10-172326, NRF-2009-352-F00042)
- Alzheimer’s Association (NIRG-10-172326, NRF-2009-352-F00042)
- National Research Foundation of Korea (NIRG-10-172326, NRF-2009-352-F00042)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Keywords
- Alzheimer's disease, amyloid-beta, metal ions, copper, zinc, metal chelation, bifunctional small molecules, amyloid-beta aggregation, structure-based drug design, chemical probes, therapeutics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
