Elucidating the influence of environmentally relevant toxic metal mixture on molecular mechanisms involved in the development of neurodegenerative diseases: In silico toxicogenomic data-mining
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2021
Authors
Živančević, Katarina
Baralić, Katarina

Jorgovanović, Dragica

Buha-Đorđević, Aleksandra

Ćurčić, Marijana

Antonijević-Miljaković, Evica

Antonijević, Biljana

Bulat, Zorica

Article (Published version)

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This in silico toxicogenomic analysis aims to: (i) testify the hypothesis about the influence of the environmentally
relevant toxic metals (lead, methylmercury (organic form of mercury), cadmium and arsenic) on molecular
mechanisms involved in amyotrophic lateral sclerosis (ALS), Parkinson’s Disease (PD) and Alzheimer’s disease
(AD) development; and (ii) demonstrate the capability of in silico toxicogenomic data-mining for distinguishing
the probable mechanisms of mixture-induced toxic effects. The Comparative Toxicogenomics Database (CTD;
http://ctd. mdibl.org) and Cytoscape software were used as the main data-mining tools in this analysis. The
results have shown that there were 7, 13 and 14 common genes for all the metals present in the mixture for each
of the selected neurodegenerative disease (ND), respectively: ALS, PD and AD. Physical interactions (68.18%)
were the most prominent interactions between the genes extracted for ALS, co-expression (60.85%) for PD and
interact...ions predicted by the server (44.30%) for AD. SOD2 gene was noted as the mutual gene for all the
selected ND. Oxidative stress, folate metabolism, vitamin B12, AGE-RAGE, apoptosis were noted as the key
disrupted molecular pathways that contribute to the neurodegenerative disease’s development. Gene ontology
analysis revealed biological processes affected by the investigated mixture (glutathione metabolic process was
listed as the most important for ALS, cellular response to toxic substance for PD, and neuron death for AD). Our
results emphasize the role of oxidative stress, particularly SOD2, in neurodegeneration triggered by environmental toxic metal mixture and give a new insight into common molecular mechanisms involved in ALS, PD and
AD pathology.
Keywords:
Neurodegeneration / Lead / Methylmercury / Cadmium / Arsenic / Toxicogenomic data-miningSource:
Environmental Research, 2021, 194Publisher:
- Elsevier
Funding / projects:
DOI: 10.1016/j.envres.2021.110727
ISSN: 0013-9351
WoS: 000632603700003
Scopus: 2-s2.0-85100143212
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Institution/Community
PharmacyTY - JOUR AU - Živančević, Katarina AU - Baralić, Katarina AU - Jorgovanović, Dragica AU - Buha-Đorđević, Aleksandra AU - Ćurčić, Marijana AU - Antonijević-Miljaković, Evica AU - Antonijević, Biljana AU - Bulat, Zorica PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3780 AB - This in silico toxicogenomic analysis aims to: (i) testify the hypothesis about the influence of the environmentally relevant toxic metals (lead, methylmercury (organic form of mercury), cadmium and arsenic) on molecular mechanisms involved in amyotrophic lateral sclerosis (ALS), Parkinson’s Disease (PD) and Alzheimer’s disease (AD) development; and (ii) demonstrate the capability of in silico toxicogenomic data-mining for distinguishing the probable mechanisms of mixture-induced toxic effects. The Comparative Toxicogenomics Database (CTD; http://ctd. mdibl.org) and Cytoscape software were used as the main data-mining tools in this analysis. The results have shown that there were 7, 13 and 14 common genes for all the metals present in the mixture for each of the selected neurodegenerative disease (ND), respectively: ALS, PD and AD. Physical interactions (68.18%) were the most prominent interactions between the genes extracted for ALS, co-expression (60.85%) for PD and interactions predicted by the server (44.30%) for AD. SOD2 gene was noted as the mutual gene for all the selected ND. Oxidative stress, folate metabolism, vitamin B12, AGE-RAGE, apoptosis were noted as the key disrupted molecular pathways that contribute to the neurodegenerative disease’s development. Gene ontology analysis revealed biological processes affected by the investigated mixture (glutathione metabolic process was listed as the most important for ALS, cellular response to toxic substance for PD, and neuron death for AD). Our results emphasize the role of oxidative stress, particularly SOD2, in neurodegeneration triggered by environmental toxic metal mixture and give a new insight into common molecular mechanisms involved in ALS, PD and AD pathology. PB - Elsevier T2 - Environmental Research T1 - Elucidating the influence of environmentally relevant toxic metal mixture on molecular mechanisms involved in the development of neurodegenerative diseases: In silico toxicogenomic data-mining VL - 194 DO - 10.1016/j.envres.2021.110727 ER -
@article{ author = "Živančević, Katarina and Baralić, Katarina and Jorgovanović, Dragica and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Antonijević-Miljaković, Evica and Antonijević, Biljana and Bulat, Zorica", year = "2021", abstract = "This in silico toxicogenomic analysis aims to: (i) testify the hypothesis about the influence of the environmentally relevant toxic metals (lead, methylmercury (organic form of mercury), cadmium and arsenic) on molecular mechanisms involved in amyotrophic lateral sclerosis (ALS), Parkinson’s Disease (PD) and Alzheimer’s disease (AD) development; and (ii) demonstrate the capability of in silico toxicogenomic data-mining for distinguishing the probable mechanisms of mixture-induced toxic effects. The Comparative Toxicogenomics Database (CTD; http://ctd. mdibl.org) and Cytoscape software were used as the main data-mining tools in this analysis. The results have shown that there were 7, 13 and 14 common genes for all the metals present in the mixture for each of the selected neurodegenerative disease (ND), respectively: ALS, PD and AD. Physical interactions (68.18%) were the most prominent interactions between the genes extracted for ALS, co-expression (60.85%) for PD and interactions predicted by the server (44.30%) for AD. SOD2 gene was noted as the mutual gene for all the selected ND. Oxidative stress, folate metabolism, vitamin B12, AGE-RAGE, apoptosis were noted as the key disrupted molecular pathways that contribute to the neurodegenerative disease’s development. Gene ontology analysis revealed biological processes affected by the investigated mixture (glutathione metabolic process was listed as the most important for ALS, cellular response to toxic substance for PD, and neuron death for AD). Our results emphasize the role of oxidative stress, particularly SOD2, in neurodegeneration triggered by environmental toxic metal mixture and give a new insight into common molecular mechanisms involved in ALS, PD and AD pathology.", publisher = "Elsevier", journal = "Environmental Research", title = "Elucidating the influence of environmentally relevant toxic metal mixture on molecular mechanisms involved in the development of neurodegenerative diseases: In silico toxicogenomic data-mining", volume = "194", doi = "10.1016/j.envres.2021.110727" }
Živančević, K., Baralić, K., Jorgovanović, D., Buha-Đorđević, A., Ćurčić, M., Antonijević-Miljaković, E., Antonijević, B.,& Bulat, Z.. (2021). Elucidating the influence of environmentally relevant toxic metal mixture on molecular mechanisms involved in the development of neurodegenerative diseases: In silico toxicogenomic data-mining. in Environmental Research Elsevier., 194. https://doi.org/10.1016/j.envres.2021.110727
Živančević K, Baralić K, Jorgovanović D, Buha-Đorđević A, Ćurčić M, Antonijević-Miljaković E, Antonijević B, Bulat Z. Elucidating the influence of environmentally relevant toxic metal mixture on molecular mechanisms involved in the development of neurodegenerative diseases: In silico toxicogenomic data-mining. in Environmental Research. 2021;194. doi:10.1016/j.envres.2021.110727 .
Živančević, Katarina, Baralić, Katarina, Jorgovanović, Dragica, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Antonijević-Miljaković, Evica, Antonijević, Biljana, Bulat, Zorica, "Elucidating the influence of environmentally relevant toxic metal mixture on molecular mechanisms involved in the development of neurodegenerative diseases: In silico toxicogenomic data-mining" in Environmental Research, 194 (2021), https://doi.org/10.1016/j.envres.2021.110727 . .