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, KatarinaBaralić, Katarina

Jorgovanović, Dragica

Buha-Đorđević, Aleksandra

Ćurčić, Marijana

Antonijević Miljaković, Evica
Antonijević, Biljana

Bulat, Zorica

Article (Published version)

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Show full item recordAbstract
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, 194, 110727-Publisher:
- Elsevier