An integrative translational framework for chemical induced neurotoxicity – a systematic review

Abstract

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 numerous in vitro, in vivo, epidemiological and in silico studies developed to test the neurotoxicity of such chemicals. This systematic review summarized the endpoints and biochemical markers generated from in vitro models, organism-based models, human studies and in silico tools 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 and in silico studies 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.

Keywords:

• In vitro
• in vivo
• epidemiology
• in silico
• translation
• neurotoxicity

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Acknowledgment

The authors gratefully acknowledge the time and efforts of the reviewers selected by the Editor and their valuable comments which, as ever, promote balanced scientific discussion. The comprehensive review process helped improve the final manuscript.

Declaration of interest

This study was financially supported by Marie Skłodowska-Curie “Neurosome Project” under the grant agreement No. 766251. V. Kumar has received funds from Health Department of Catalonia Government trough “Pla Estratègic de Recerca i Innovació en salut” (PERIS 2016-2020). This publication reflects only the authors’ views and they have no potential competing financial interests. The Community and other funding organizations are not liable for any use made of the information contained therein. The authors confirm that the present review and conclusions drawn reflect the professional work product of the authors, and, over the last 5 years, none of them have engaged in any legal, regulatory or advocacy activities related to this review’s content.