The Case for Abandoning Therapeutic Chelation of Copper Ions in Alzheimer's Disease.
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TLDR
The author plays the devil's advocate, questioning the experimental evidence, the dogma, and the value of therapeutic chelation, with a major focus on copper ions.Abstract:
The ‘therapeutic chelation’ approach to treating Alzheimer’s disease (AD) evolved from the metals hypothesis, with the premise that small molecules can be designed to prevent transition metal-induced amyloid deposition and oxidative stress within the AD brain. Over more than twenty years, countless in vitro studies have been devoted to characterizing metal binding, its effect on Aβ aggregation, ROS production and in vitro toxicity. Despite a lack of evidence for any clinical benefit, the conjecture that therapeutic chelation is effective approach for treating AD remains widespread. Here, the author plays the devil’s advocate, questioning the experimental evidence, the dogma and the value of therapeutic chelation, with a major focus on the role of copper ions.read more
Citations
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Journal ArticleDOI
Oxidative stress and the amyloid beta peptide in Alzheimer's disease.
Clémence Cheignon,M. Tomas,M. Tomas,Dominique Bonnefont-Rousselot,Peter Faller,Christelle Hureau,Christelle Hureau,Fabrice Collin,Fabrice Collin +8 more
TL;DR: This review highlights the existing link between oxidative stress and AD, and the consequences towards the Aβ peptide and surrounding molecules in terms of oxidative damage, along with the implication of metal ions in AD.
Journal ArticleDOI
Critical Review of Exposure and Effects: Implications for Setting Regulatory Health Criteria for Ingested Copper.
Alicia A. Taylor,Joyce S. Tsuji,Michael R. Garry,Margaret E. McArdle,William L. Goodfellow,William J. Adams,Charles A. Menzie +6 more
TL;DR: Limits in the existing United States and international guidance for determining an oral reference dose for essential metals like copper were identified and an alternative method using categorical regression analysis to develop an optimal dose was reviewed for interpreting an oral RfD for copper.
Journal ArticleDOI
Copper and Zinc Dysregulation in Alzheimer’s Disease
TL;DR: The role of AD-related neurodegeneration and cognitive decline triggered by the imbalance of two endogenous metals: copper and zinc is focused on.
Journal ArticleDOI
Role of Copper in the Onset of Alzheimer's Disease Compared to Other Metals.
TL;DR: The involvement of copper in AD is controversial, as some studies show a copper deficiency in AD, and consequently a need to enhance copper levels, while other data point to copper overload and therefore a needs to reduce copper levels.
Journal ArticleDOI
Copper signalling: causes and consequences.
TL;DR: A deeper understanding of of the regulatory effects of copper on neuro-glia coupling via polyamine metabolism may reveal novel copper signalling functions and new directions for therapeutic intervention in brain disorders associated with aberrant copper metabolism.
References
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Alzheimer's disease: the amyloid cascade hypothesis
John Hardy,Gerald A. Higgins +1 more
TL;DR: An extensive catalog of genes that act in a migrating cell is provided, unique molecular functions involved in nematode cell migration are identified, and similar functions in humans are suggested.
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Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein
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TL;DR: A purified protein derived from the twisted beta-pleated sheet fibrils in cerebrovascular amyloidosis associated with Alzheimer's disease has been isolated and Amino acid sequence analysis and a computer search reveals this protein to have no homology with any protein sequenced thus far.
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Amyloid plaque core protein in Alzheimer disease and Down syndrome
Colin L. Masters,Gail Simms,Nicola A. Weinman,Gerd Multhaup,Brian L. McDonald,Konrad Beyreuther +5 more
TL;DR: The shared 4-kDa subunit indicates a common origin for the amyloids of the plaque core and of the congophilic angiopathy of Alzheimer disease and Down syndrome.
Book
Data for Biochemical Research
TL;DR: Methods for the detection of biochemical compounds on paper and thin layer chromatograms, with some notes on separation Ion exchange, gel filtration, and affinity chromatography media isotopic data.
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Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides
TL;DR: The amyloid beta protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration.
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