An attempt to elucidate the role of iron and zinc ions in development of Alzheimer’s and Parkinson’s diseases

Wojtunik-Kulesza, Karolina; Oniszczuk, Anna; Waksmundzka‐Hajnos, Monika

doi:10.1016/j.biopha.2018.12.140

Cited by 70 publications

(27 citation statements)

References 117 publications

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“…Previous papers, however, presented few methods based on metal ion reduction. The reduction process in our organism is important because of its contribution to neurodegeneration [3,14]. Among the methods to investigate this reduction effect is FRAP, which is based on reducing Fe 3+ to Fe 2+ .…”

Section: Discussionmentioning

confidence: 99%

“…This results from the fact that the ion is responsible for the aggregation of hyperphosphorylated tau, and is associated with neurofibrillary tangles, as well as progressive supranuclear palsy (PSP). Reduction of Fe 3+ to Fe 2+ can reverse this process and solubilize tau species characteristic of neurodegeneration [3]. Among methods used to determine the reduction ability of Fe 3+ to Fe 2+ is ferric-reducing antioxidant power (FRAP), a colorimetric method which uses the ability of antioxidants to reduce the colorless [Fe 3+ -(2,4,6-Tris(2-pirydyl)-s-triazine) 2 ] 3+ complex to the intensively blue-colored complex [Fe 2+ -(TPTZ) 2 ] 2+ in acidic medium [4].…”

Section: Introductionmentioning

confidence: 99%

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Approach to Optimization of FRAP Methodology for Studies Based on Selected Monoterpenes

Wojtunik-Kulesza

2020

Molecules

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Terpenes, wide-spread secondary plant metabolites, constitute important parts of many natural compounds that hold various biological activities, including antioxidant, calming, antiviral, and analgesic activities. Due to their high volatility and low solubility in water, studies of compounds based on terpenes are difficult, and methodologies must be adjusted to their specific characteristics. Considering the significant influence of iron ions on dementia development, the activity of terpenes in reducing Fe3+ represents an important area to be determined. Previously obtained results were unreliable because ferric-reducing antioxidant power (FRAP) methodology was not adjusted regarding studying terpenes. Taking this fact into account, the aim of this study was to optimize the method for monoterpene assessment. The study included three modifications, namely, (1) slightly adjusting the entire FRAP procedure, (2) replacing methanol with other solvents (heptane, butanone, or ethyl acetate), and (3) adding Tween 20. Additionally, a thin layer chromatography (TLC) -FRAP assay was performed. The obtained results revealed significant improvement in the reduction activity of selected terpenes (linalool, α-phellandrene, and α-terpinene) in studies with Tween 20, whereas replacing methanol with other solvents did not show the expected effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Approach to Optimization of FRAP Methodology for Studies Based on Selected Monoterpenes

Wojtunik-Kulesza

2020

Molecules

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“…When the intracellular iron concentrations increase, it upregulates the translation of APP by virtue of IREs in the 5'-UTR mRNA, thereby increasing the amount of APP protein and potentially producing more Aβ (Becerril-Ortega et al, 2014;Peters et al, 2015;Telling et al, 2017). Additionally, iron also directly binds to Aβ in His6, His13, and His14 amino acid residues, thereby strengthening the neurotoxicity of Aβ (Uranga and Salvador, 2018;Wojtunik-Kulesza et al, 2019).…”

Section: Iron Metabolism Linking With Ad Pathologymentioning

confidence: 99%

Iron Metabolism, Ferroptosis, and the Links With Alzheimer’s Disease

2020

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Iron is an essential transition metal for numerous biologic processes in mammals. Iron metabolism is regulated via several coordination mechanisms including absorption, utilization, recycling, and storage. Iron dyshomeostasis can result in intracellular iron retention, thereby damaging cells, tissues, and organs through free oxygen radical generation. Numerous studies have shown that brain iron overload is involved in the pathological mechanism of neurodegenerative disease including Alzheimer's disease (AD). However, the underlying mechanisms have not been fully elucidated. Ferroptosis, a newly defined iron-dependent form of cell death, which is distinct from apoptosis, necrosis, autophagy, and other forms of cell death, may provide us a new viewpoint. Here, we set out to summarize the current knowledge of iron metabolism and ferroptosis, and review the contributions of iron and ferroptosis to AD.

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“…Also, high labile Mn levels have been reported to increase oxidative stress [42]. Labile Zn 2+ is more abundant in healthy brain cells, as it is released by neural activity at many central excitatory synapses [48], but still this metal ion was related to oxidative stress [49]. Labile metal ion pools can also undergo a pathogenic relation with α-syn.…”

Section: Parkinson's Disease and Metal Ionsmentioning

confidence: 99%

“…Many mechanisms have been considered and reviewed for the damage induced by Cu [44], Fe [49,[64][65][66], Mn [67] and Zn [49] under PD conditions; in several cases, oxidative damage, metal dyshomeostasis and α-syn aggregation have been demonstrated to be strictly related to each other.…”

Section: Metal Ionmentioning

confidence: 99%

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

Tosato

Marco

2019

Biomolecules

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The present review reports a list of approximately 800 compounds which have been used, tested or proposed for Parkinson’s disease (PD) therapy in the year range 2014–2019 (April): name(s), chemical structure and references are given. Among these compounds, approximately 250 have possible or established metal-chelating properties towards Cu(II), Cu(I), Fe(III), Fe(II), Mn(II), and Zn(II), which are considered to be involved in metal dyshomeostasis during PD. Speciation information regarding the complexes formed by these ions and the 250 compounds has been collected or, if not experimentally available, has been estimated from similar molecules. Stoichiometries and stability constants of the complexes have been reported; values of the cologarithm of the concentration of free metal ion at equilibrium (pM), and of the dissociation constant Kd (both computed at pH = 7.4 and at total metal and ligand concentrations of 10–6 and 10–5 mol/L, respectively), charge and stoichiometry of the most abundant metal–ligand complexes existing at physiological conditions, have been obtained. A rigorous definition of the reported amounts is given, the possible usefulness of this data is described, and the need to characterize the metal–ligand speciation of PD drugs is underlined.

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An attempt to elucidate the role of iron and zinc ions in development of Alzheimer’s and Parkinson’s diseases

Cited by 70 publications

References 117 publications

Approach to Optimization of FRAP Methodology for Studies Based on Selected Monoterpenes

Approach to Optimization of FRAP Methodology for Studies Based on Selected Monoterpenes

Iron Metabolism, Ferroptosis, and the Links With Alzheimer’s Disease

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

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