Human-induced pluripotent stems cells as a model to dissect the selective neurotoxicity of methylmercury
Methylmercury (MeHg) is a potent neurotoxicant affecting both the developing and mature central nervous system (CNS) with apparent indiscriminate disruption of multiple homeostatic pathways. However, genetic and environmental modifiers contribute significant variability to neurotoxicity associated w...
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| Published in | Biochimica et biophysica acta. General subjects Vol. 1863; no. 12; p. 129300 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.12.2019
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0304-4165 1872-8006 1872-8006 |
| DOI | 10.1016/j.bbagen.2019.02.002 |
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| Abstract | Methylmercury (MeHg) is a potent neurotoxicant affecting both the developing and mature central nervous system (CNS) with apparent indiscriminate disruption of multiple homeostatic pathways. However, genetic and environmental modifiers contribute significant variability to neurotoxicity associated with human exposures. MeHg displays developmental stage and neural lineage selective neurotoxicity. To identify mechanistic-based neuroprotective strategies to mitigate human MeHg exposure risk, it will be critical to improve our understanding of the basis of MeHg neurotoxicity and of this selective neurotoxicity. Here, we propose that human-based pluripotent stem cell cellular approaches may enable mechanistic insight into genetic pathways that modify sensitivity of specific neural lineages to MeHg-induced neurotoxicity. Such studies are crucial for the development of novel disease modifying strategies impinging on MeHg exposure vulnerability.
•Methylmercury (MeHg) is a potent neurotoxicant affecting both the developing and mature central nervous system (CNS).•MeHg displays developmental stage and neural lineage selective neurotoxicity.•Stem cells may enable mechanistic insight into genetic pathways that modify sensitivity of specific neural lineages to MeHg.•Genetic and environmental modifiers contribute significant variability to neurotoxicity associated with human exposures. |
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| AbstractList | Methylmercury (MeHg) is a potent neurotoxicant affecting both the developing and mature central nervous system (CNS) with apparent indiscriminate disruption of multiple homeostatic pathways. However, genetic and environmental modifiers contribute significant variability to neurotoxicity associated with human exposures. MeHg displays developmental stage and neural lineage selective neurotoxicity. To identify mechanistic-based neuroprotective strategies to mitigate human MeHg exposure risk, it will be critical to improve our understanding of the basis of MeHg neurotoxicity and of this selective neurotoxicity. Here, we propose that human-based pluripotent stem cell cellular approaches may enable mechanistic insight into genetic pathways that modify sensitivity of specific neural lineages to MeHg-induced neurotoxicity. Such studies are crucial for the development of novel disease modifying strategies impinging on MeHg exposure vulnerability. Methylmercury (MeHg) is a potent neurotoxicant affecting both the developing and mature central nervous system (CNS) with apparent indiscriminate disruption of multiple homeostatic pathways. However, genetic and environmental modifiers contribute significant variability to neurotoxicity associated with human exposures. MeHg displays developmental stage and neural lineage selective neurotoxicity. To identify mechanistic-based neuroprotective strategies to mitigate human MeHg exposure risk, it will be critical to improve our understanding of the basis of MeHg neurotoxicity and of this selective neurotoxicity. Here, we propose that human-based pluripotent stem cell cellular approaches may enable mechanistic insight into genetic pathways that modify sensitivity of specific neural lineages to MeHg-induced neurotoxicity. Such studies are crucial for the development of novel disease modifying strategies impinging on MeHg exposure vulnerability. •Methylmercury (MeHg) is a potent neurotoxicant affecting both the developing and mature central nervous system (CNS).•MeHg displays developmental stage and neural lineage selective neurotoxicity.•Stem cells may enable mechanistic insight into genetic pathways that modify sensitivity of specific neural lineages to MeHg.•Genetic and environmental modifiers contribute significant variability to neurotoxicity associated with human exposures. Methylmercury (MeHg) is a potent neurotoxicant affecting both the developing and mature central nervous system (CNS) with apparent indiscriminate disruption of multiple homeostatic pathways. However, genetic and environmental modifiers contribute significant variability to neurotoxicity associated with human exposures. MeHg displays developmental stage and neural lineage selective neurotoxicity. To identify mechanistic-based neuroprotective strategies to mitigate human MeHg exposure risk, it will be critical to improve our understanding of the basis of MeHg neurotoxicity and of this selective neurotoxicity. Here, we propose that human-based pluripotent stem cell cellular approaches may enable mechanistic insight into genetic pathways that modify sensitivity of specific neural lineages to MeHg-induced neurotoxicity. Such studies are crucial for the development of novel disease modifying strategies impinging on MeHg exposure vulnerability.Methylmercury (MeHg) is a potent neurotoxicant affecting both the developing and mature central nervous system (CNS) with apparent indiscriminate disruption of multiple homeostatic pathways. However, genetic and environmental modifiers contribute significant variability to neurotoxicity associated with human exposures. MeHg displays developmental stage and neural lineage selective neurotoxicity. To identify mechanistic-based neuroprotective strategies to mitigate human MeHg exposure risk, it will be critical to improve our understanding of the basis of MeHg neurotoxicity and of this selective neurotoxicity. Here, we propose that human-based pluripotent stem cell cellular approaches may enable mechanistic insight into genetic pathways that modify sensitivity of specific neural lineages to MeHg-induced neurotoxicity. Such studies are crucial for the development of novel disease modifying strategies impinging on MeHg exposure vulnerability. |
| ArticleNumber | 129300 |
| Author | Aschner, Michael Bowman, Aaron B. Prince, Lisa M. |
| AuthorAffiliation | 1 School of Health Sciences, Purdue University, West Lafayette, IN 47907-2051, United States 2 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, United States |
| AuthorAffiliation_xml | – name: 1 School of Health Sciences, Purdue University, West Lafayette, IN 47907-2051, United States – name: 2 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, United States |
| Author_xml | – sequence: 1 givenname: Lisa M. surname: Prince fullname: Prince, Lisa M. organization: School of Health Sciences, Purdue University, West Lafayette, IN 47907-2051, United States – sequence: 2 givenname: Michael surname: Aschner fullname: Aschner, Michael organization: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, United States – sequence: 3 givenname: Aaron B. surname: Bowman fullname: Bowman, Aaron B. email: Bowma117@purdue.edu organization: School of Health Sciences, Purdue University, West Lafayette, IN 47907-2051, United States |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30742955$$D View this record in MEDLINE/PubMed |
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| Keywords | Selective neurotoxicity Human pluripotent stem cells Methylmercury Neurodevelopmental toxicity |
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| Snippet | Methylmercury (MeHg) is a potent neurotoxicant affecting both the developing and mature central nervous system (CNS) with apparent indiscriminate disruption of... |
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| SubjectTerms | central nervous system Genomic Imprinting - drug effects Human pluripotent stem cells Humans Induced Pluripotent Stem Cells - metabolism Induced Pluripotent Stem Cells - pathology Methylmercury methylmercury compounds Methylmercury Compounds - toxicity Models, Biological Neurodevelopmental toxicity neurotoxicity Neurotoxicity Syndromes - genetics Neurotoxicity Syndromes - metabolism Neurotoxicity Syndromes - pathology neurotoxins Neurotoxins - toxicity risk Selective neurotoxicity stem cells |
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| Title | Human-induced pluripotent stems cells as a model to dissect the selective neurotoxicity of methylmercury |
| URI | https://dx.doi.org/10.1016/j.bbagen.2019.02.002 https://www.ncbi.nlm.nih.gov/pubmed/30742955 https://www.proquest.com/docview/2209602626 https://www.proquest.com/docview/2221019118 https://pubmed.ncbi.nlm.nih.gov/PMC6689259 https://www.ncbi.nlm.nih.gov/pmc/articles/6689259 |
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