bims-metalz 2024-06-09 papers

Issue of 2024–06–09
five papers selected by
Mikaila Chetty, Goa University

Front Aging Neurosci. 2024 ;16 1414956

P-hydroxybenzaldehyde protects Caenorhabditis elegans from oxidative stress and β-amyloid toxicity.

Xingzhi Yu, Jie Tao, Tian Xiao, Xiaohua Duan.

Introduction: Gastrodia elata is the dried tuber of the orchid Gastrodia elata Bl. It is considered a food consisting of a source of precious medicinal herbs, whose chemical composition is relatively rich. Gastrodia elata and its extracted fractions have been shown to have neuroprotective effects. P-hydroxybenzaldehyde (p-HBA), as one of the main active components of Gastrodia elata, has anti-inflammatory, antioxidative stress, and cerebral protective effects, which has potential for the treatment of Alzheimer's disease (AD). The aim of this study was to verify the role of p-HBA in AD treatment and to investigate its mechanism of action in depth based using the Caenorhabditis elegans (C. elegans) model.
Methods: In this study, we used paralysis, lifespan, behavioral and antistress experiments to investigate the effects of p-HBA on AD and aging. Furthermore, we performed reactive oxygen species (ROS) assay, thioflavin S staining, RNA-seq analysis, qPCR validation, PCR Array, and GFP reporter gene worm experiment to determine the anti-AD effects of p-HBA, as well as in-depth studies on its mechanisms.
Results: p-HBA was able to delay paralysis, improve mobility and resistance to stress, and delay aging in the AD nematode model. Further mechanistic studies showed that ROS and lipofuscin levels, Aβ aggregation, and toxicity were reduced after p-HBA treatment, suggesting that p-HBA ameliorated Aβ-induced toxicity by enhancing antioxidant and anti-aging activity and inhibiting Aβ aggregation. p-HBA had a therapeutic effect on AD by improving stress resistance, as indicated by the down-regulation of NLP-29 and UCR-11 expression and up-regulation of PQN-75 and LYS-3 expression. In addition, the gene microarray showed that p-HBA treatment played a positive role in genes related to AD, anti-aging, ribosomal protein pathway, and glucose metabolism, which were collectively involved in the anti-AD mechanism of p-HBA. Finally, we also found that p-HBA promoted nuclear localization of DAF-16 and increased the expression of SKN-1, SOD-3, and GST-4, which contributed significantly to inhibition of Aβ toxicity and enhancement of antioxidative stress.
Conclusion: Our work suggests that p-HBA has some antioxidant and anti-aging activities. It may be a viable candidate for the treatment and prevention of Alzheimer's disease.

Keywords: Alzheimer’s disease; Aβ protein; Caenorhabditis elegans; neuroprotection; oxidative stress; p-hydroxybenzaldehyde

DOI: https://doi.org/10.3389/fnagi.2024.1414956

Sci Total Environ. 2024 May 31. pii: S0048-9697(24)03788-4. [Epub ahead of print]940 173641

Zinc oxide/graphene oxide nanocomposites specifically remediated Cd-contaminated soil via reduction of bioavailability and ecotoxicity of Cd.

Yang Li, Lei Cheng, Baolin Yang, Yuting Ding, Yanan Zhao, Yuanyuan Wu, Yaguang Nie, Yun Liu, An Xu.

From both environment and health perspectives, sustainable management of ever-growing soil contamination by heavy metal is posing a serious global concern. The potential ecotoxicity of cadmium (Cd) to soil and ecosystem seriously threatens human health. Developing efficient, specific, and long-term remediation technology for Cd-contaminated soil is impending to synchronously minimize the bioavailability and ecotoxicity of Cd. In the present study, zinc oxide/graphene oxide nanocomposite (ZnO/GO) was developed as a novel amendment for remediating Cd-contaminated soil. Our results showed that ZnO/GO effectively decreased the available soil Cd content, and increased pH and cation exchange capacity (CEC) in both Cd-spiked standard soil and Cd-contaminated mine field soil through the interaction between ZnO/GO and soil organic acids. Using Caenorhabditis elegans (C. elegans) as a model organism for soil safety evaluation, ZnO/GO was further proved to decrease the ecotoxicity of Cd-contaminated soil. Specifically, ZnO/GO promoted Cd excretion and declined Cd storage in C. elegans by increasing the expression of gene ttm-1 and decreasing the level of gene cdf-2, which were responsible for Cd transportation and Cd accumulation, respectively. Moreover, the efficacy of ZnO/GO in remediating the properties and ecotoxicity of Cd-contaminated soil increased gradually with the time gradient, and could maintain a long-term effect after reaching the optimal remediation efficiency. Our findings established a specific and long-term strategy to simultaneously improve soil properties and reduce ecotoxicity of Cd-contaminated soil, which might provide new insights into the potential application of ZnO/GO in soil remediation for both ecosystem and human health.

Keywords: Bioavailability; Cadmium; Ecotoxicity; Soil remediation; ZnO/GO

DOI: https://doi.org/10.1016/j.scitotenv.2024.173641

Mol Neurobiol. 2024 Jun 05.

Selenium Nanoparticles as Neuroprotective Agents: Insights into Molecular Mechanisms for Parkinson's Disease Treatment.

Suganiya Umapathy, Ieshita Pan, Praveen Kumar Issac, Meenakshi Sundaram Kishore Kumar, Jayant Giri, Ajay Guru, Jesu Arockiaraj.

Oxidative stress and the accumulation of misfolded proteins in the brain are the main causes of Parkinson's disease (PD). Several nanoparticles have been used as therapeutics for PD. Despite their therapeutic potential, these nanoparticles induce multiple stresses upon entry. Selenium (Se), an essential nutrient in the human body, helps in DNA formation, stress control, and cell protection from damage and infections. It can also regulate thyroid hormone metabolism, reduce brain damage, boost immunity, and promote reproductive health. Selenium nanoparticles (Se-NPs), a bioactive substance, have been employed as treatments in several disciplines, particularly as antioxidants. Se-NP, whether functionalized or not, can protect mitochondria by enhancing levels of reactive oxygen species (ROS) scavenging enzymes in the brain. They can also promote dopamine synthesis. By inhibiting the aggregation of tau, α-synuclein, and/or Aβ, they can reduce the cellular toxicities. The ability of the blood-brain barrier to absorb Se-NPs which maintain a healthy microenvironment is essential for brain homeostasis. This review focuses on stress-induced neurodegeneration and its critical control using Se-NP. Due to its ability to inhibit cellular stress and the pathophysiologies of PD, Se-NP is a promising neuroprotector with its anti-inflammatory, non-toxic, and antimicrobial properties.

Keywords: Aging; Antioxidant; Dopamine; Mitochondrial dysfunction; Oxidative stress; Parkinson’s disease (PD); Protein aggregation; Selenium nanoparticles (Se-NPs)

DOI: https://doi.org/10.1007/s12035-024-04253-x

Int J Nanomedicine. 2024 ;19 4857-4875

Brain Targeting Nanomedicines: Pitfalls and Promise.

Aleksandr Kakinen, Yuhao Jiang, Thomas Paul Davis, Tambet Teesalu, Mart Saarma.

Brain diseases are the most devastating problem among the world's increasingly aging population, and the number of patients with neurological diseases is expected to increase in the future. Although methods for delivering drugs to the brain have advanced significantly, none of these approaches provide satisfactory results for the treatment of brain diseases. This remains a challenge due to the unique anatomy and physiology of the brain, including tight regulation and limited access of substances across the blood-brain barrier. Nanoparticles are considered an ideal drug delivery system to hard-to-reach organs such as the brain. The development of new drugs and new nanomaterial-based brain treatments has opened various opportunities for scientists to develop brain-specific delivery systems that could improve treatment outcomes for patients with brain disorders such as Alzheimer's disease, Parkinson's disease, stroke and brain tumors. In this review, we discuss noteworthy literature that examines recent developments in brain-targeted nanomedicines used in the treatment of neurological diseases.

Keywords: blood-brain barrier; brain delivery; cancer; nanoparticle; neurodegenerative diseases; stroke; targeted delivery

DOI: https://doi.org/10.2147/IJN.S454553

Chem Commun (Camb). 2024 Jun 05.

Inhibition of fibril formation by polyphenols: molecular mechanisms, challenges, and prospective solutions.

Shilpa Sharma, Shashank Deep.

Fibril formation is a key feature in neurodegenerative diseases like Alzheimer's, Parkinson's, and systemic amyloidosis. Polyphenols, found in plant-based foods, show promise in inhibiting fibril formation and disrupting disease progression. The ability of polyphenols to break the amyloid fibrils of many disease-linked proteins has been tested in numerous studies. Polyphenols have their distinctive mechanism of action. They behave differently on various events in the aggregation pathway. Their action also differs for different proteins. Some polyphenols only inhibit the formation of fibrils whereas others break the preformed fibrils. Some break the fibrils into smaller species, and some change them to other morphologies. This article delves into the intricate molecular mechanisms underlying the inhibitory effects of polyphenols on fibrillogenesis, shedding light on their interactions with amyloidogenic proteins and the disruption of fibril assembly pathways. However, addressing the challenges associated with solubility, stability, and bioavailability of polyphenols is crucial. The current strategies involve nanotechnology to improve the solubility and bioavailability, thus showing the potential to enhance the efficacy of polyphenols as therapeutics. Advancements in structural biology, computational modeling, and biophysics have provided insights into polyphenol-fibril interactions, offering hope for novel therapies for neurodegenerative diseases and amyloidosis.

DOI: https://doi.org/10.1039/d4cc00822g