IMR Press / FBL / Volume 28 / Issue 9 / DOI: 10.31083/j.fbl2809204
Open Access Review
From Mechanisms to Implications: Understanding the Molecular Neurotoxicity of Titanium Dioxide Nanoparticles
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1 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2 Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, 150003 Yaroslavl, Russia
3 Center of Bioelementology and Human Ecology, IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia
4 Department of Medical Elementology, Peoples’ Friendship University of Russia (RUDN University), 117198 Moscow, Russia
5 Faculty of Sciencies, National Autonomous University of Mexico, 04510 Mexico City, Mexico
6 Department of Toxicology ‘Akademik Danilo Soldatović’, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia
7 Department of Pharmacology, Howard University College of Medicine, Washington, DC 20059, USA
8 Department of Toxicology, School of Public Health, Guangxi Medical University, 530021 Nanning, Guangxi, China
9 Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, 530021 Nanning, Guangxi, China
10 Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, 212013 Zhenjiang, Jiangsu, China
11 Departamento de Farmacología Otto Orsingher, Instituto de Farmacología Experimental de Córdoba-Consejo Nacional de Investigaciones Técnicas (IFEC-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, X5000HUA Córdoba, Argentina
*Correspondence: (Alexey A. Tinkov)
Front. Biosci. (Landmark Ed) 2023, 28(9), 204;
Submitted: 19 June 2023 | Revised: 3 August 2023 | Accepted: 24 August 2023 | Published: 15 September 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Titanium dioxide nanoparticles (TiO2NPs) are widely produced and used nanoparticles. Yet, TiO2NP exposure may possess toxic effects to different cells and tissues, including the brain. Recent studies significantly expanded the understanding of the molecular mechanisms underlying TiO2NP neurotoxicity implicating a number of both direct and indirect mechanisms. In view of the significant recent progress in research on TiO2NP neurotoxicity, the objective of the present study is to provide a narrative review on the molecular mechanisms involved in its neurotoxicity, with a special focus on the studies published in the last decade. The existing data demosntrate that although TiO2NP may cross blood-brain barrier and accumulate in brain, its neurotoxic effects may be mediated by systemic toxicity. In addition to neuronal damage and impaired neurogenesis, TiO2NP exposure also results in reduced neurite outgrowth and impaired neurotransmitter metabolism, especially dopamine and glutamate. TiO2NP exposure was also shown to promote α-synuclein and β-amyloid aggregation, thus increasing its toxicity. Recent findings also suggest that epigenetic effects and alterations in gut microbiota biodiversity contribute to TiO2NP neurotoxicity. Correspondingly, in vivo studies demosntrated that TiO2NPs induce a wide spectrum of adverse neurobehavioral effects, while epidemiological data are lacking. In addition, TiO2NPs were shown to promote neurotoxic effects of other toxic compounds. Here we show the contribution of a wide spectrum of molecular mechanisms to TiO2NP-induced neurotoxicity; yet, the role of TiO2NP exposure in adverse neurological outcomes in humans has yet to be fully appreciated.

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
Fig. 1.
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