Metals in Alzheimer's and Parkinson's Diseases
Abstract
There has been steadily growing interest in the participation of metal ions (especially, zinc, copper, and iron) in neurobiological processes, such as the regulation of synaptic transmission. Recent descriptions of the release of zinc and copper in the cortical glutamatergic synapse, and influencing the response of the NMDA receptor underscore the relevance of understanding the inorganic milieu of the synapse to neuroscience. Additionally, major neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease, are characterized by elevated tissue iron, and miscompartmentalization of copper and zinc (e.g. accumulation in amyloid). Increasingly sophisticated medicinal chemistry approaches, which correct these metal abnormalities without causing systemic disturbance of these essential minerals, are being tested. These small molecules show promise of being disease-modifying.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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 can reduce metal-mediated Aβ aggregation, ROS formation, and neurotoxicity in vitro.
“Given the recognized interactions of Aβ with transition metal ions, several studies have shown that metal chelators can reduce the metal-mediated Aβ aggregation, ROS formation, and neurotoxicity in vitro.43–45”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ<sub>42</sub>Peptide (2012) · cites this paper as [45]
The non-specific chelator clioquinol (CQ) showed decreased Aβ aggregate formation that resulted in improved cognition in clinical trials.
“For example, the non-specific chelator clioquinol (CQ) showed decreased Aβ aggregate formation that resulted in improved cognition in clinical trials.24,25,43–45”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ<sub>42</sub>Peptide (2012) · cites this paper as [45]
Cites
1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · see citing works
RetractedBush, A. (2000) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(99)00073-3 · Cited by 731 · see citing works
Self-citationMetals and Alzheimer's disease
Adlard, P. A., & Bush, A. I. (2006) · Journal of Alzheimer's Disease · doi:10.3233/jad-2006-102-303 · Cited by 324 · see citing works
Self-citationMaeda, J., Ji, B., Irie, T., Tomiyama, T., Maruyama, M., Okauchi, T., Staufenbiel, M., Iwata, N., Ono, M., Saido, T. C., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.0673-07.2007 · Cited by 300 · see citing works
Esposito, L., Raber, J., Kekonius, L., Yan, F., Yu, G.-Q., Bien-Ly, N., Puoliväli, J., Scearce-Levie, K., Masliah, E., & Mucke, L. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0482-06.2006 · Cited by 254 · see citing works
Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation
Chinnery, P. F., Crompton, D. E., Birchall, D., Jackson, M. J., Coulthard, A., Lombes, A., Quinn, N., Wills, A., Fletcher, N., Mottershead, J. P., et al. (2006) · Brain · doi:10.1093/brain/awl319 · Cited by 205 · see citing works
Youdim, M. B. H., Fridkin, M., & Zheng, H. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0143-x · Cited by 123 · see citing works
Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease
Hochstrasser, H., Bauer, P., Walter, U., Behnke, S., Spiegel, J., Csoti, I., Zeiler, B., Bornemann, A., Pahnke, J., Becker, G., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000144276.29988.c3 · Cited by 111 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Scott, L. E., & Orvig, C. (2009) · Chemical Reviews · doi:10.1021/cr9000176 · Cited by 332 · see citing works
Mechanisms of Brain Iron Transport: Insight into Neurodegeneration and CNS Disorders
Mills, E., Dong, X.-P., Wang, F., & Xu, H. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.09.140 · Cited by 309 · see citing works
Rodríguez-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
Small 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 · see citing works
Bifunctional 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
Sarell, C. J., Wilkinson, S. R., & Viles, J. H. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.171355 · Cited by 199 · see citing works
Yan, J., Hu, J., Liu, A., He, L., Li, X., & Wei, H. (2017) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.02.048 · Cited by 65 · see citing works
Ocular manifestations of Alzheimer's disease in animal models
Parnell, M., Guo, L., Abdi, M., & Cordeiro, M. F. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/786494 · Cited by 56 · see citing works
Braymer, J. J., DeToma, A. S., Choi, J.-S., Ko, K. S., & Lim, M. H. (2011) · International Journal of Alzheimer’s Disease · doi:10.4061/2011/623051 · Cited by 50 · 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].”
BackgroundInfluentialUranga, R. M., & Salvador, G. A. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/2850341 · Cited by 48 · see citing works
The chelation targeting metal–Aβ40 aggregates may lead to formation of Aβ40 oligomers
Zhang, Y., Chen, L.-Y., Yin, W.-X., Yin, J., Zhang, S.-B., & Liu, C.-L. (2011) · Dalton Transactions · doi:10.1039/c1dt00020a · Cited by 26 · see citing works
Bacci, A., Runfola, M., Sestito, S., & Rapposelli, S. (2021) · Antioxidants · doi:10.3390/antiox10030367 · Cited by 23 · see citing works
Tripathi, S., Kumari, U., & Mitra Mazumder, P. (2020) · Journal of Food Biochemistry · doi:10.1111/jfbc.13504 · Cited by 19 · see citing works
Tomasello, M. F., Di Rosa, M. C., Naletova, I., Sciacca, M. F. M., Giuffrida, A., Maccarrone, G., & Attanasio, F. (2025) · Bioinorganic Chemistry and Applications · doi:10.1155/bca/4226220 · Cited by 3 · see citing works
“Among the main and consistent features of AD, oxidative stress and imbalances in the metal ions homeostasis have a critical role [10, 11].”
- Authors
- Barnham, K. J., & Bush, A. I.
- Affiliations
- Mental Health Research Institute (AU)
- Corresponding author
- Bush, Ashley I
- Venue
- Current Opinion in Chemical Biology
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 12
- Issue
- 2
- Pages
- 222-228
- ISSN
- 1367-5931 (ISSN-L)
- OpenAlex
- W2069856306
- Cited by
- 695
- References
- 8
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 20 · 2023: 24 · 2022: 29 · 2021: 39 · 2020: 47 · 2019: 32 · 2018: 47 · 2017: 49 · 2016: 34 · 2015: 50 · 2014: 45 · 2013: 48 · 2012: 47
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Australian Research Council
- National Health and Medical Research Council
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- Alzheimer's disease, Parkinson's disease, metal ions, zinc, copper, iron, synaptic transmission, NMDA receptor, glutamatergic synapses, amyloid, neurodegeneration, metal chelators, disease-modifying therapy
- MeSH terms
- Aging, Alzheimer Disease, Animals, Humans, Metals, Parkinson Disease, Protein Binding, Amyloid beta-Protein Precursor
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
