TY - JOUR
T1 - From Mechanisms to Implications
T2 - Understanding the Molecular Neurotoxicity of Titanium Dioxide Nanoparticles
AU - Aschner, Michael
AU - Skalny, Anatoly V.
AU - Santamaria, Abel
AU - Djordjevic, Aleksandra Buha
AU - Tizabi, Yousef
AU - Jiang, Yueming
AU - Lu, Rongzhu
AU - Virgolini, Miriam B.
AU - Tinkov, Alexey A.
N1 - Publisher Copyright:
Copyright: © 2023 The Author(s). Published by IMR Press.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - brain
KW - nanoparticle
KW - neurodegeneration
KW - neuroinflammation
KW - neurotoxicity
KW - titanium
UR - http://www.scopus.com/inward/record.url?scp=85172868856&partnerID=8YFLogxK
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U2 - 10.31083/j.fbl2809204
DO - 10.31083/j.fbl2809204
M3 - Review article
C2 - 37796714
AN - SCOPUS:85172868856
SN - 2768-6701
VL - 28
JO - Frontiers in Bioscience - Landmark
JF - Frontiers in Bioscience - Landmark
IS - 9
M1 - 204
ER -