Journal
CRITICAL REVIEWS IN TOXICOLOGY
Volume 50, Issue 5, Pages 424-438Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10408444.2020.1763253
Keywords
In vitro; in vivo; epidemiology; in silico; translation; neurotoxicity
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Funding
- Marie Sklodowska-Curie Neurosome Project [766251]
- Health Department of Catalonia Government trough Pla Estrategic de Recerca i Innovacio en salut (PERIS 2016-2020)
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Many chemicals in day-to-day and industrial usage have the ability to cross the blood-brain barrier and develop neurotoxicity in humans. There are numerousin vitro,in vivo, epidemiological andin silicostudies developed to test the neurotoxicity of such chemicals. This systematic review summarized the endpoints and biochemical markers generated fromin vitromodels, organism-based models, human studies andin silicotools and how they are used to translate the data for risk assessment of neurotoxic chemicals. Increased evidence about different biomarkers through genomics and proteomics has developed data related to genes and proteins facilitating some understanding about the molecular mechanism of neurotoxicity. Fluid-based biomarkers such as those found in serum, plasma and urine from human studies act as indirect endpoints for neurotoxicity. Meanwhile, with improvement in knowledge of molecular mechanisms and different biomarkers, there is a potential to develop a translational platform that can integrate the biological data from different studies mechanistically and thereby translated across intra and interspecies for neurotoxicity assessment. Further, this review proposed an integrative translational framework combining experimental andin silicostudies like toxicokinetic models and integrative systems biology to assess the chemicals for neurotoxicity. This framework can be used to predict the inherent risk of neurotoxicity and extend to such chemicals where less experimental data exists.
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