The Impact of Inhaled Ambient Ultrafine Particulate Matter on Developing Brain: Potential Importance of Elemental Contaminants DOI Open Access
Deborah A. Cory‐Slechta, Marissa Sobolewski, Elena Marvin

et al.

Toxicologic Pathology, Journal Year: 2019, Volume and Issue: 47(8), P. 976 - 992

Published: Oct. 14, 2019

Epidemiological studies report associations between air pollution (AP) exposures and several neurodevelopmental disorders including autism, attention deficit disorder, cognitive delays. Our in mice of postnatal (human third trimester brain equivalent) to concentrated ambient ultrafine particles (CAPs) provide biological plausibility for these associations, producing numerous neuropathological behavioral features disorders, male-biased vulnerability. These findings raise questions about the specific components AP that underlie its neurotoxicity, which our suggest could involve trace elements as candidate neurotoxicants. X-ray fluorescence analyses CAP chamber filters confirm contamination by multiple elements, iron (Fe) sulfur (S). Correspondingly, laser ablation inductively coupled plasma mass spectrometry brains male indicates marked postexposure elevations Fe S other elements. Elevations particular are consistent with potential ferroptotic, oxidative stress, altered antioxidant capacity-based mechanisms CAPs-induced supported observations increased serum oxidized glutathione neuronal cell death nucleus accumbens no corresponding significant increase caspase-3, following exposures. Understanding role element contaminants particulate matter a source neurotoxicity is critical public health protection.

Language: Английский

Oxidative stress and the amyloid beta peptide in Alzheimer’s disease DOI Creative Commons
Clémence Cheignon, Mireia Tomas, Dominique Bonnefont–Rousselot

et al.

Redox Biology, Journal Year: 2017, Volume and Issue: 14, P. 450 - 464

Published: Oct. 19, 2017

Oxidative stress is known to play an important role in the pathogenesis of a number diseases. In particular, it linked etiology Alzheimer's disease (AD), age-related neurodegenerative and most common cause dementia elderly. Histopathological hallmarks AD are intracellular neurofibrillary tangles extracellular formation senile plaques composed amyloid-beta peptide (Aβ) aggregated form along with metal-ions such as copper, iron or zinc. Redox active metal ions, for example can catalyze production Reactive Oxygen Species (ROS) when bound amyloid-β (Aβ). The ROS thus produced, particular hydroxyl radical which reactive one, may contribute oxidative damage on both Aβ itself surrounding molecule (proteins, lipids, …). This review highlights existing link between AD, consequences towards molecules terms damage. addition, implication ions their interaction redox properties leading discussed, vitro vivo oxidation peptide, at molecular level.

Language: Английский

Citations

1814
Critical Review of Exposure and Effects: Implications for Setting Regulatory Health Criteria for Ingested Copper DOI Creative Commons

Alicia A. Taylor,

Joyce S. Tsuji,

Michael R. Garry

et al.

Environmental Management, Journal Year: 2019, Volume and Issue: 65(1), P. 131 - 159

Published: Dec. 12, 2019

Abstract Decades of study indicate that copper oral exposures are typically not a human health concern. Ingesting high levels soluble salts can cause acute gastrointestinal symptoms and, in uncommon cases, liver toxicity susceptible individuals with repeated exposure. This focused toxicological review evaluated the current literature since last comprehensive reviews (2007–2010). Our identified limitations existing United States and international guidance for determining an reference dose (RfD) essential metals like copper. Instead, alternative method using categorical regression analysis to develop optimal considers deficiency, toxicity, integrates information from animal studies was reviewed interpreting RfD We also considered subchronic or chronic genetic susceptibility dysregulation leading rare occurrences other organ elevated Based on this approach, 0.04 mg Cu/kg/day would be protective adults children. is possible exposure allows background dietary exposures. intended patients disorders sensitivity within typical nutritional intake ranges, nor it those excessive supplement intake. Less mineral forms soil have reduced bioavailability as compared more water diet, which should risk assessments

Language: Английский

Citations

426
Copper Dyshomeostasis in Neurodegenerative Diseases—Therapeutic Implications DOI Open Access
Grażyna Gromadzka, Beata Tarnacka,

Anna Flaga

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(23), P. 9259 - 9259

Published: Dec. 4, 2020

Copper is one of the most abundant basic transition metals in human body. It takes part oxygen metabolism, collagen synthesis, and skin pigmentation, maintaining integrity blood vessels, as well iron homeostasis, antioxidant defense, neurotransmitter synthesis. may also be involved cell signaling participate modulation membrane receptor-ligand interactions, control kinase related phosphatase functions, many cellular pathways. Its role important controlling gene expression nucleus. In nervous system particular, copper myelination, by modulating synaptic activity excitotoxic death cascades induced neurotrophic factors, for various neuronal functions. Current data suggest that both excess levels deficiency can harmful, careful homeostatic important. This knowledge opens up an new area potential therapeutic interventions based on supplementation or removal neurodegenerative diseases including Wilson’s disease (WD), Menkes (MD), Alzheimer’s (AD), Parkinson’s (PD), others. However, much remains to discovered, how regulate homeostasis prevent neurodegeneration, when chelate copper, supplement it.

Language: Английский

Citations

237
Copper and Zinc Dysregulation in Alzheimer’s Disease DOI
Stefano L. Sensi, Alberto Granzotto,

Mariacristina Siotto

et al.

Trends in Pharmacological Sciences, Journal Year: 2018, Volume and Issue: 39(12), P. 1049 - 1063

Published: Oct. 20, 2018

Language: Английский

Citations

235
Role of Copper in the Onset of Alzheimer’s Disease Compared to Other Metals DOI Creative Commons
Soghra Bagheri, Rosanna Squitti, Thomas Haertlé

et al.

Frontiers in Aging Neuroscience, Journal Year: 2018, Volume and Issue: 9

Published: Jan. 23, 2018

Alzheimer's disease (AD) is a neurodegenerative disorder that characterized by amyloid plaques in patients' brain tissue. The are mainly made of β-amyloid peptides and trace elements including Zn

Language: Английский

Citations

192
Copper signalling: causes and consequences DOI Creative Commons
Julianna Kardos, László Héja, Ágnes Simon

et al.

Cell Communication and Signaling, Journal Year: 2018, Volume and Issue: 16(1)

Published: Oct. 22, 2018

Copper-containing enzymes perform fundamental functions by activating dioxygen (O

Language: Английский

Citations

181
Current Biomedical Use of Copper Chelation Therapy DOI Open Access
Silvia Baldari, Giuliana Di Rocco, Gabriele Toietta

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(3), P. 1069 - 1069

Published: Feb. 6, 2020

Copper is an essential microelement that plays important role in a wide variety of biological processes. concentration has to be finely regulated, as any imbalance its homeostasis can induce abnormalities. In particular, excess copper the etiopathogenesis genetic disease Wilson's syndrome, neurological and neurodegenerative pathologies such Alzheimer's Parkinson's diseases, idiopathic pulmonary fibrosis, diabetes, several forms cancer. chelating agents are among most promising tools keep at physiological levels. this review, we focus on relevant compounds experimentally clinically evaluated for their ability counteract deregulation. provide general overview main disorders characterized by pathological increase levels, summarizing principal therapies adopted clinical trials.

Language: Английский

Citations

144
Metallobiology and therapeutic chelation of biometals (copper, zinc and iron) in Alzheimer’s disease: Limitations, and current and future perspectives DOI Creative Commons
Kehinde D. Fasae, Amos O. Abolaji, Tolulope R. Faloye

et al.

Journal of Trace Elements in Medicine and Biology, Journal Year: 2021, Volume and Issue: 67, P. 126779 - 126779

Published: May 15, 2021

Alzheimer's disease (AD) is the most prevalent cause of cognitive impairment and dementia worldwide. The pathobiology has been studied in form several hypotheses, ranging from oxidative stress, amyloid-beta (Aβ) aggregation, accumulation tau forming neurofibrillary tangles (NFT) through metal dysregulation homeostasis, dysfunction cholinergic system, to inflammatory autophagic mechanism. However, none these hypotheses led confirmed diagnostics or approved cure for disease. This review aimed as a basic an encyclopedic short course into metals AD discusses advances chelation strategies developments adopted treatment Since there accumulating evidence role both biometal dyshomeostasis (iron (Fe), copper (Cu), zinc (Zn)) metal-amyloid interactions that lead pathogenesis AD, this focuses on unraveling therapeutic have considered disease, aiming sequester free protein-bound ions reducing cerebral burden. Promising compounds possessing chemically modified moieties evolving multi-target ligands used anti-AD drug candidates are also covered. Several multidirectional multifaceted studies therapeutics show need improved synthesis, screening, analysis be able effectively present chelating drugs. Most limitations their physicochemical properties; some enhance redistribution ions, while others indirectly activate signaling pathways AD. process vivo still needs established design potential bi-functionally well inhibit Aβ aggregation by competing with metal-induced damage neurotoxicity may signal bright end chelation-based

Language: Английский

Citations

109
N‐Terminal Cu‐Binding Motifs (Xxx‐Zzz‐His, Xxx‐His) and Their Derivatives: Chemistry, Biology and Medicinal Applications DOI
Paulina González, Karolina Bossak‐Ahmad, Ewelina Stefaniak

et al.

Chemistry - A European Journal, Journal Year: 2018, Volume and Issue: 24(32), P. 8029 - 8041

Published: Jan. 16, 2018

Abstract Peptides and proteins with N‐terminal amino acid sequences NH 2 ‐Xxx‐His (XH) ‐Xxx‐Zzz‐His (XZH) form well‐established high‐affinity Cu II ‐complexes. Key examples are Asp‐Ala‐His (in serum albumin) Gly‐His‐Lys, the wound healing factor. This opens a straightforward way to add ‐binding site almost any peptide or protein, by chemical recombinant approaches. Thus, these motifs, in particular, have been used equip peptides multitude of functions based on redox activity Cu, including nuclease, protease, glycosidase, oxygen activation properties, useful anticancer antimicrobial drugs. More recent research suggests novel biological functions, mainly inertness XZH, like PET imaging (with 64 Cu), chelation therapies (for instance Alzheimer's disease other types neurodegeneration), antioxidant units, transporters strong binding. Review gives an overview properties Cu‐XH ‐XZH motifs discusses pros cons vastly different applications, how they could be improved depending application.

Language: Английский

Citations

121
Biomedical applications of copper ionophores DOI
Valentina Oliveri

Coordination Chemistry Reviews, Journal Year: 2020, Volume and Issue: 422, P. 213474 - 213474

Published: Aug. 1, 2020

Language: Английский

Citations

121