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Review
. 2016 Mar;53:223-235.
doi: 10.1016/j.neuro.2016.02.002. Epub 2016 Feb 8.

Toxicity Mechanisms of Arsenic That Are Shared With Neurodegenerative Diseases and Cognitive Impairment: Role of Oxidative Stress and Inflammatory Responses

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Review

Toxicity Mechanisms of Arsenic That Are Shared With Neurodegenerative Diseases and Cognitive Impairment: Role of Oxidative Stress and Inflammatory Responses

Claudia Escudero-Lourdes. Neurotoxicology. .

Abstract

Arsenic (As) is a worldwide naturally occurring metalloid. Human chronic exposure to inorganic As compounds (iAs), which are at the top of hazardous substances (ATSDR, 2013), is associated with different diseases including cancer and non- cancerous diseases. The neurotoxic effects of iAs and its methylated metabolites have been demonstrated in exposed populations and experimental models. Impaired cognitive abilities have been described in children and adults chronically exposed to iAs through drinking water. Even though different association studies failed to demonstrate that As causes neurodegenerative diseases, several toxicity mechanisms of iAs parallel those mechanisms associated with neurodegeneration, including oxidative stress and inflammation, impaired protein degradation, autophagy, and intracellular accumulation, endoplasmic reticulum stress, and mitochondrial dysfunction. Additionally, different reports have shown that specifically in brain tissue, iAs and its metabolites induce hyper-phosphorylation of the tau protein and over-regulation of the amyloid precursor protein, impaired neurotransmitters synthesis and synaptic transmission, increased glutamate receptors activation, and decreased glutamate transporters expression. Interestingly, increased and sustained pro-inflammatory responses mediated by cytokines and related factors, seems to be the triggering factor for all of such cellular pathological effects. Therefore, this review proposes that iAs-associated cognitive impairment could be the result of the activation of pro-inflammatory responses in the brain tissue, which also may favor neurodegeneration or increase the risk for neurodegenerative diseases in exposed human populations.

Keywords: Arsenic; Inflammation; Neurodegeneration; Oxidative stress.

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