Metals, oxidative stress and neurodegeneration: a focus on iron, manganese and mercury.

Given the global abundance and environmental persistence, exposure of humans and (aquatic) animals to micro- and nanoplastics is unavoidable. Current evidence indicates that micro- and nanoplastics can be taken up by aquatic organism as well as by mammals. Upon uptake, micro- and nanoplastics can reach the brain, although there is limited information regarding the number of particles that reaches the brain and the potential neurotoxicity of these small plastic particles. Earlier studies indicated that metal and metal-oxide nanoparticles, such as gold (Au) and titanium dioxide (TiO2) nanoparticles, can also reach the brain to exert a range of neurotoxic effects. Given the similarities between these chemically inert metal(oxide) nanoparticles and plastic particles, this review aims to provide an overview of the reported neurotoxic effects of micro- and nanoplastics in different species and in vitro. The combined data, although fragmentary, indicate that exposure to micro- and nanoplastics can induce oxidative stress, potentially resulting in cellular damage and an increased vulnerability to develop neuronal disorders. Additionally, exposure to micro- and nanoplastics can result in inhibition of acetylcholinesterase activity and altered neurotransmitter levels, which both may contribute to the reported behavioral changes. Currently, a systematic comparison of the neurotoxic effects of different particle types, shapes, sizes at different exposure concentrations and durations is lacking, but urgently needed to further elucidate the neurotoxic hazard and risk of exposure to micro- and nanoplastics.

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The plastic brain: neurotoxicity of micro- and nanoplastics

Alzheimer’s disease (AD) remains an incurable disease and lacks efficient diagnostic methods. Most AD treatments have focused on amyloid-β (Aβ) targeted therapy; however, it is time to consider the alternative theranostics due to accumulated findings of weak correlation between Aβ deposition and cognition, as well as the failures of Phase III clinical trial on Aβ targeted therapy. Recent studies have shown that the tau pathway is closely associated with clinical development of AD symptoms, which might be a potential therapeutic target. We herein construct a methylene blue (MB, a tau aggregation inhibitor) loaded nanocomposite (CeNC/IONC/MSN-T807), which not only possesses high binding affinity to hyperphosphorylated tau but also inhibits multiple key pathways of tau-associated AD pathogenesis. We demonstrate that these nanocomposites can relieve the AD symptoms by mitigating mitochondrial oxidative stress, suppressing tau hyperphosphorylation, and preventing neuronal death both in vitro and in vivo. The m...

Tau-Targeted Multifunctional Nanocomposite for Combinational Therapy of Alzheimer's Disease.

Background In the recent decade, iron oxide nanoparticles (IONPs) have been proposed for several applications in the central nervous system (CNS), including targeting amyloid beta (Aβ) in the arteries, inhibiting the microglial cells, delivering drugs, and increasing contrast in magnetic resonance imaging. Conversely, a notable number of studies have reported the role of iron in neurodegenerative diseases. Therefore, this study has reviewed the recent studies to determine whether IONPs iron can threaten the cellular viability same as iron. Results Iron contributes in Fenton’s reaction and produces reactive oxygen species (ROS). ROS cause to damage the macromolecules and organelles of the cell via oxidative stress. Iron accumulation and oxidative stress are able to aggregate some proteins, including Aβ and α-synuclein, which play a critical role in Alzheimer’s and Parkinson’s diseases, respectively. Iron accumulation, oxidative stress, and protein aggregation make a positive feedback loop, which can be toxic for the cell. The release of iron ions from IONPs may result in iron accumulation in the targeted tissue, and thus, activate the positive feedback loop. However, the levels of IONPs induced toxicity depend on the size, concentration, surface charge, and the type of coating and functional groups of IONPs. Conclusion IONPs depending on their properties can lead to iron accumulation, oxidative stress and protein aggregation in the neural cells. Therefore, in order to apply IONPs in the CNS, the consideration of IONPs properties is crucial.

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Iron oxide nanoparticles may damage to the neural tissue through iron accumulation, oxidative stress, and protein aggregation

Are iron oxide nanoparticles safe? Current knowledge and future perspectives.

It has recently been reported that iron oxide nanoparticles (Fe 3 O 4 -NPs, 30 nm) have the ability to translocate directly from the olfactory nerve to the brain The striatum and hippocampus are important structures in the brain and are associated with the development of Parkinson's and Alzheimer's diseases Therefore, it is critical to evaluate Fe 3 O 4 -NPs and their potential to confer striatum and hippocampus neurotoxicity This study focuses on the effects of Fe 3 O 4 -NPs on the striatum and hippocampus, including oxidative injury and the accumulation and retention of Fe 3 O 4 -NPs This study also explores the molecular mechanism of oxidative damage in dopaminergic neurons; we were able to assess the neurotoxic effects of Fe 3 O 4 -NPs by incubating dopaminergic neurons with radioactive Fe 3 O 4 -NPs A regional distribution of Fe 3 O 4 -NPs was observed in rat brains after the particles were intranasally instilled for seven days The particles were found to be deposited at particularly high concentrations in the rat striata and hippocampi Over half of the Fe 3 O 4 -NPs were retained in the striata for a minimum of 14 days, and may have induced oxidative damage to the region However, no injuries were observed in the hippocampi These in vitro studies demonstrate that Fe 3 O 4 -NPs may decrease neuron viability, trigger oxidative stress, and activate JNK- and p53-mediated pathways to regulate the cell cycle and apoptosis These results also suggest that environmental exposure to Fe 3 O 4 -NPs may play a role in the development of neurodegenerative diseases

Jie Wu

Papers

Neurotoxic potential of iron oxide nanoparticles in the rat brain striatum and hippocampus

Method for preparing I mark product for ferroferric oxide nanoparticles and application thereof