Mechanisms of lead and manganese neurotoxicity

Neal, April P.; Guilarte, Tomás R.

doi:10.1039/c2tx20064c

Cited by 175 publications

(110 citation statements)

References 272 publications

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“…[60] . Consistent with these observations, evidence summarized recently in our lab and others increasingly indicates that Pb 2+ neurotoxicity is related to interference with synaptic activity [61,62] , which is likely associated with disruption of Zn 2+ and Ca 2+ -dependent functions by Pb 2+ [23,24] .…”

Section: Metal Ion Coordination In Proteinssupporting

confidence: 66%

“…However, there is a growing body of research suggesting that the ionic displacement model does not adequately address the complex interactions between metals and proteins, and the mechanisms which may lead to cellular toxicity and interference with important physiological and neurological processes. Several recent review papers have highlighted research suggesting multiple mechanisms associated with metal toxicity, particularly with respect to disruption of synaptic activity and neural pathways by substitution of Pb 2+ for Ca 2+ and Zn 2+ in proteins [1,[23][24][25] . [26] by influx and efflux through membrane permeable Ca 2+ channels, regulated by various control mechanisms and events, including membrane depolarization, external agonists, and depletion of internal stores in the sarcoplasmic reticulum (SR) and endoplasmic reticulum (ER).…”

Section: Introductionmentioning

confidence: 99%

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Pb(II) Disruption of Synaptic Activity Through Ca(II)- and Zn(II)-binding Proteins

2017

Neurotransmitter

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Section: Metal Ion Coordination In Proteinssupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Pb(II) Disruption of Synaptic Activity Through Ca(II)- and Zn(II)-binding Proteins

2017

Neurotransmitter

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“…However, when homeostatic regulation of Mn absorption or excretion is disrupted, Mn concentrations can increase in the blood and accumulation in the brain (Neal & Guilarte, 2013). Excessive accumulation of Mn in the brain can trigger adverse CNS dysfunctions known as manganism, an extrapyramidal motor disorder similar to Parkinsonism.…”

Section: Manganesementioning

confidence: 99%

“…For non-occupational exposure, the primary route of Mn is via ingestion (e.g. Mn contamination of drinking water) (Neal & Guilarte, 2013 The present document has been produced and adopted by the bodies identified above as authors. This task has been carried out exclusively by the authors in the context of a contract between the European Food Safety Authority and the authors, awarded following a tender procedure.…”

Section: Manganesementioning

confidence: 99%

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

Choi¹,

Polcher²,

Joas³

2016

EFSA Supporting Publications

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This report presents the outcomes of a systematic review (SR) identifying the mechanisms and chemicals involved in the pathogenesis of Parkinson's disease (PD) and childhood leukaemia (CL). This work serves as a basis for defining and mapping the causal linkages between a molecular initiating event (MIE) and a final adverse outcome (AO) that are relevant for the development of a prototype adverse outcome pathway (AOP) for assessing risk factors for PD and CL. Search for literature from 1990 to present was conducted using Web of Science, PubMed and TOXNET, and relevant references were selected using established inclusion/exclusion criteria and ranked using a set of quality control factors.For PD, 7,384 individual references were identified to be relevant for PD pathogenesis and chemicals associated with PD. Dopaminergic neurodegeneration in the substantia nigra leading to locomotor deficits was identified as the AO in PD. Other identified key events in PD pathogenesis include mitochondrial dysfunction, cellular accumulation of alpha-synuclein and oxidative stress. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone and paraquat are some chemicals identified to be associated with PD pathogenesis.For CL, 1,988 individual references were identified to be relevant for CL pathogenesis and chemicals associated with CL. Chromosomal translocation, genetic damage/mutation and hyperdiploidy are considered as driving forces of CL. Except for infant leukaemia, CL pathogenesis requires a 'two-hit' model with an initiating event occurring in utero followed by a secondary hit potentially occurring after birth. Potential MIEs leading to these driving mechanisms include aberrant DNA topoisomerase II activity and erroneous DNA repair. Epigenetics appears to also play an influential role in CL pathogenesis. Benzene, bioflavonoids and organophosphates are some chemicals identified to be implicated in CL pathogenesis.The challenges of developing AOPs for these two diseases and the data gaps identified from the outcomes of this SR are also elaborated in this report. The present document has been produced and adopted by the bodies identified above as authors. This task has been carried out exclusively by the authors in the context of a contract between the European Food Safety Authority and the authors, awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. KEY WORDSSystematic Review, Parkinson Disease, Childhood Leukaemia, Pathogenesis, Chemicals, Pesticides, Adverse Outcome Pathway SUMMARYThe aim of this project was to perform a systematic review (SR) to collect relevant publications related to the mechanisms involved in the pathogenesis of Parkinson's disease (PD)...

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“…Manganese is a mineral element that is both nutritionally essential and potentially toxic for human health in high levels [37]. Studies in children have suggested that extremely high levels of manganese exposure may changes in behavior and decreases in the ability to learn and remember [29].…”

Section: Manganese (Mn)mentioning

confidence: 99%

First determination of mineral composition of the leaf Chicory (Cichorium intybus L.) used in human nourishment in the Midwest of Brazil and comparasion with dietary reference intakes for children and adults

Rosa¹,

Lopes²,

Nascimento³

et al. 2017

int arch med

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Introduction: Radicchio (Cichorium intybus L.) is a leaf chicory and is grown as a leaf vegetable which usually has white-veined red or purple leaves and it belongs to the Asteraceae family. In several countries is consumed mainly as salad, but no studies on their elemental composition has been done, principally in Brazil. Objective:The aim of present work was to measure the macroelements (Na, K, Ca, Mg and P) and microelements (Cr, Cu, Fe, Mn, Mo, Zn, Al, Cd, Ni, Co and Si) in the leaf Chicory used as human nourishment in the Campo Grande, State of Mato Grosso do Sul, Brazil.Method: Chemical digests of samples were prepared using HNO 3 and H 2 O 2 and then placed in the microwave digestion system. After digestion, the concentrations of the elements in leaf chicory were determined by the technique of Inductively Coupled Plasma -Optical Emission Spectrometer (ICP-OES, Thermo Scientific -iCAP 6000 Series). Results obtained of the concentrations of leaf chicory were compared with the dietary reference intakes.Results: Detected concentration of macroelements in leaf chicory decreases in the order: K > P > Ca > Mg > Na. As well as the con- IntroductionThe nutrition is one of the main factors of concern and are a major cause of mortality in old age [1]. According the World Health Organization (WHO), the malnutrition contribute to more than one third of all child deaths. Due to rising food prices, lack of access to highly nutritious foods is a common cause of malnutrition. There are others factors that contribute to malnutrition such as inadequate breastfeeding and the wrong foods [2]. The WHO estimate in 2013 was that 5.2 million deaths worldwide would be attributable to inadequate consumption of fruits and vegetables [3]. At present, only a small minority of the world's population consumes the average intake of fruits and vegetables recommended by countries or health services. In fact, studies have found that regular intake of fruits and vegetables reduces the risk of cardiovascular diseases, cancers, diabetes and hypertension [4].In fact, vegetables can be healthy alternatives to human food. Vegetables are important sources of many nutrients and are recommended for supplementation of diet in human. In this context, Brazil has great number of vegetables and wide variety of fruits that is not yet well investigated [5]. Vegetables as Cichorium intybus Linnaeus (leaf chicory) are important foods in the diet of the Brazilian people as well as in others countries [6]. Chicory is a traditional European horticultural crop [7]. In Brazil and Italy, the leaf chicory is called "radicchio", being consumed mainly as salad. Radicchio production has increased in Brazil, where it is currently considered an important vegetable due to high proportion of the agricultural income. Radicchio is a perennial, and has a quick growing with red-colored leafy ( Figure 2) [8]. In recent work [6], the botanical classification the genus Cichorium is reported and a detailed description of the most important cultivated biotypes is prese...

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Mechanisms of lead and manganese neurotoxicity

Cited by 175 publications

References 272 publications

Pb(II) Disruption of Synaptic Activity Through Ca(II)- and Zn(II)-binding Proteins

Pb(II) Disruption of Synaptic Activity Through Ca(II)- and Zn(II)-binding Proteins

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

First determination of mineral composition of the leaf Chicory (Cichorium intybus L.) used in human nourishment in the Midwest of Brazil and comparasion with dietary reference intakes for children and adults

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