TY - JOUR
T1 - Arsenic-induced neurotoxicity
T2 - a mechanistic appraisal
AU - Garza-Lombó, Carla
AU - Pappa, Aglaia
AU - Panayiotidis, Mihalis I.
AU - Gonsebatt, María E.
AU - Franco, Rodrigo
N1 - Funding Information:
This work was supported by the National Institutes of Health Grant P20RR17675 Centers of Biomedical Research Excellence (COBRE), the Research Council, and the Office of Research at the University of Nebraska-Lincoln.
Publisher Copyright:
© 2019, Society for Biological Inorganic Chemistry (SBIC).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Arsenic is a metalloid found in groundwater as a byproduct of soil/rock erosion and industrial and agricultural processes. This xenobiotic elicits its toxicity through different mechanisms, and it has been identified as a toxicant that affects virtually every organ or tissue in the body. In the central nervous system, exposure to arsenic can induce cognitive dysfunction. Furthermore, iAs has been linked to several neurological disorders, including neurodevelopmental alterations, and is considered a risk factor for neurodegenerative disorders. However, the exact mechanisms involved are still unclear. In this review, we aim to appraise the neurotoxic effects of arsenic and the molecular mechanisms involved. First, we discuss the epidemiological studies reporting on the effects of arsenic in intellectual and cognitive function during development as well as studies showing the correlation between arsenic exposure and altered cognition and mental health in adults. The neurotoxic effects of arsenic and the potential mechanisms associated with neurodegeneration are also reviewed including data from experimental models supporting epidemiological evidence of arsenic as a neurotoxicant. Next, we focused on recent literature regarding arsenic metabolism and the molecular mechanisms that begin to explain how arsenic damages the central nervous system including, oxidative stress, energy failure and mitochondrial dysfunction, epigenetics, alterations in neurotransmitter homeostasis and synaptic transmission, cell death pathways, and inflammation. Outlining the specific mechanisms by which arsenic alters the cell function is key to understand the neurotoxic effects that convey cognitive dysfunction, neurodevelopmental alterations, and neurodegenerative disorders.
AB - Arsenic is a metalloid found in groundwater as a byproduct of soil/rock erosion and industrial and agricultural processes. This xenobiotic elicits its toxicity through different mechanisms, and it has been identified as a toxicant that affects virtually every organ or tissue in the body. In the central nervous system, exposure to arsenic can induce cognitive dysfunction. Furthermore, iAs has been linked to several neurological disorders, including neurodevelopmental alterations, and is considered a risk factor for neurodegenerative disorders. However, the exact mechanisms involved are still unclear. In this review, we aim to appraise the neurotoxic effects of arsenic and the molecular mechanisms involved. First, we discuss the epidemiological studies reporting on the effects of arsenic in intellectual and cognitive function during development as well as studies showing the correlation between arsenic exposure and altered cognition and mental health in adults. The neurotoxic effects of arsenic and the potential mechanisms associated with neurodegeneration are also reviewed including data from experimental models supporting epidemiological evidence of arsenic as a neurotoxicant. Next, we focused on recent literature regarding arsenic metabolism and the molecular mechanisms that begin to explain how arsenic damages the central nervous system including, oxidative stress, energy failure and mitochondrial dysfunction, epigenetics, alterations in neurotransmitter homeostasis and synaptic transmission, cell death pathways, and inflammation. Outlining the specific mechanisms by which arsenic alters the cell function is key to understand the neurotoxic effects that convey cognitive dysfunction, neurodevelopmental alterations, and neurodegenerative disorders.
KW - Metalloid
KW - Neurotoxicity
KW - Oxidative stress
KW - Redox homeostasis
KW - iAs
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U2 - 10.1007/s00775-019-01740-8
DO - 10.1007/s00775-019-01740-8
M3 - Review article
C2 - 31748979
AN - SCOPUS:85075376401
SN - 0949-8257
VL - 24
SP - 1305
EP - 1316
JO - Journal of Biological Inorganic Chemistry
JF - Journal of Biological Inorganic Chemistry
IS - 8
ER -