bims-metalz 2024-05-19 papers

bims-metalz

Biomed News

on Metabolic causes of Alzheimer’s disease

Issue of 2024–05–19
eleven papers selected by
Mikaila Chetty, Goa University

C. elegans Hedgehog-related proteins are tissue- and substructure-specific components of the cuticle and pre-cuticle.
Silver Nanoparticle-Based Drug Delivery Systems in the Fight Against COVID-19: Enhancing Efficacy, Reducing Toxicity, and Improving Drug Bioavailability.
Photodynamic treatment increases the lifespan and oxidative stress resistance of Caenorhabditis elegans.
Adsorption of Heavy Metal Ions on Alginate-Based Magnetic Nanocomposite Adsorbent Beads.
Exposure to 6-PPD quinone causes damage on mitochondrial complex I/II associated with lifespan reduction in Caenorhabditis elegans.
Rebalancing the motor circuit restores movement in a Caenorhabditis elegans model for TDP-43 toxicity.
Circulating Cell Free DNA and DNA Double-Strand Breakage in Alzheimer's Disease.
An automatic measurement method for the response of Caenorhabditis elegans to chemicals.
Amyloid-β and Phosphorylated Tau are the Key Biomarkers and Predictors of Alzheimer's Disease.
Multifunctional Nanocarrier for Synergistic Treatment of Alzheimer's Disease by Inhibiting β-Amyloid Aggregation and Scavenging Reactive Oxygen Species.
Natural products in the management of neurodegenerative diseases.

Genetics. 2024 May 13. pii: iyae081. [Epub ahead of print]

C. elegans Hedgehog-related proteins are tissue- and substructure-specific components of the cuticle and pre-cuticle.

Nicholas D Serra, Chelsea B Darwin, Meera V Sundaram.

  In C. elegans, expanded families of divergent Hedgehog-related and Patched-related proteins promote numerous processes ranging from epithelial and sense organ development to pathogen responses to cuticle shedding during the molt cycle. The molecular functions of these proteins have been mysterious since nematodes lack a canonical Hedgehog signaling pathway. Here we show that Hedgehog-related proteins are components of the cuticle and pre-cuticle apical extracellular matrices that coat, shape, and protect external epithelia. Of four Hedgehog-related proteins imaged, two (GRL-2 and GRL-18) stably associated with the cuticles of specific tubes and two (GRL-7 and WRT-10) labelled pre-cuticle substructures such as furrows or alae. We found that wrt-10 mutations disrupt cuticle alae ridges, consistent with a structural role in matrix organization. We hypothesize that most nematode Hedgehog-related proteins are apical extracellular matrix components, a model that could explain many of the reported functions for this family. These results highlight ancient connections between Hedgehog proteins and the extracellular matrix and suggest that any signaling roles of C. elegans Hedgehog-related proteins will be intimately related to their matrix association.

Keywords:   C. elegans ; Hedgehog; aECM; cuticle; matrix

DOI:  https://doi.org/10.1093/genetics/iyae081
J Drug Target. 2024 May 14. 1-21

Silver Nanoparticle-Based Drug Delivery Systems in the Fight Against COVID-19: Enhancing Efficacy, Reducing Toxicity, and Improving Drug Bioavailability.

Mehdi Yoosefian, Hanieh Sabaghian.

  Nanoparticles (NPs) have played a pivotal role in various biomedical applications, spanning from sensing to drug delivery, imaging, and antiviral therapy. The therapeutic utilization of NPs in clinical trials was established in the early 1990s. Silver nanoparticles (AgNPs) possess antimicrobial, anticancer, and antiviral properties, which make them a possible antiviral drug to combat the COVID-19 virus. Free radicals and reactive oxygen species (ROS) are produced by AgNPs, which causes apoptosis induction and prevents viral contamination. The shape and size of AgNPs can influence their interactions and biological activities. Therefore, it is recommended that silver nanoparticles (AgNPs) be used as a valuable tool in the management of COVID-19 pandemic. These nanoparticles possess strong antimicrobial properties, allowing them to penetrate and destroy microbial cells. Additionally, the toxicity level of nanoparticles depends on the administered dose, and surface modifications are necessary to reduce toxicity, preventing direct interaction between metal surfaces and cells. By utilizing silver nanoparticles, drugs can be targeted to specific areas in the body. For example, in the case of COVID-19, antiviral drugs can be stimulated as nanoparticles in the lungs to accelerate disease recovery. Nanoparticle-based systems have the capability to transport drugs and treat specific body parts. This review offers an examination of silver nanoparticle-based drug delivery systems for combatting COVID-19, with the objective of boosting the bioavailability of existing medications, decreasing their toxicity and raising their efficiency.

Keywords:  SARS-CoV-2; Silver nanoparticles; bioavailability; drug delivery systems; toxicity

DOI:  https://doi.org/10.1080/1061186X.2024.2356147
Free Radic Biol Med. 2024 May 14. pii: S0891-5849(24)00458-1. [Epub ahead of print]

Photodynamic treatment increases the lifespan and oxidative stress resistance of Caenorhabditis elegans.

Uyen Tran Tu Nguyen, Esther Youn, Tram Anh Ngoc Le, Ngoc Minh Ha, Son Hung Tran, Sohyun Lee, Jin Wook Cha, Jin-Soo Park, Hak Cheol Kwon, Kyungsu Kang.

  Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can be employed for targeted tissue destruction in cancer treatment or antimicrobial therapy. However, it remains unknown whether lower amounts of ROS produced by mild photodynamic therapy increase lifespan and stress resistance at the organism level. Here, we introduce a novel photodynamic treatment (PDTr) that uses 20 μM hypericin, a photosensitizer that originates from Hypericum perforatum, and orange light (590 nm, 5.4 W/m2, 1 min) to induce intracellular ROS formation (ROS), thereby resulting in lifespan extension and improved stress resistance in C. elegans. The PDTr-induced increase in longevity was abrogated by N-acetyl cysteine, suggesting the hormetic response was driven by prooxidative mechanisms. PDTr activated the translocation of SKN-1/NRF-2 and DAF-16/FOXO, leading to elevated expression of downstream oxidative stress-responsive genes, including ctl-1, gst-4, and sod-3. In summary, our findings suggest a novel PDTr method that extends the lifespan of C. elegans under both normal and oxidative stress conditions through the activation of SKN-1 and DAF-16 via the involvement of many antioxidant genes.

Keywords:  Caenorhabditis elegans; Hypericin; hormesis; lifespan; photodynamic treatment

DOI:  https://doi.org/10.1016/j.freeradbiomed.2024.05.023
Materials (Basel). 2024 Apr 23. pii: 1942. [Epub ahead of print]17(9):

Adsorption of Heavy Metal Ions on Alginate-Based Magnetic Nanocomposite Adsorbent Beads.

Eleonora Russo, Paolo Sgarbossa, Simone Gelosa, Sabrina Copelli, Elisabetta Sieni, Marco Barozzi.

  Graphene oxide and its magnetic nanoparticle-based composites are a well-known tool to remove heavy metals from wastewater. Unfortunately, one of the major issues in handling such small particles consists of their difficult removal from treated wastewater (even when their magnetic properties are exploited), due to their very small diameter. One possible way to overcome this problem is to embed them in a macroscopic biopolymer matrix, such as alginate or chitosan beads. In this way, the adsorbent becomes easier to handle and can be used to build, for example, a packed column, as in a traditional industrial adsorber. In this work, the removal performances of two different embedded magnetic nanocomposite adsorbents (MNAs) are discussed. The first type of MNA is based on ferrite magnetic nanoparticles (MNPs) generated by coprecipitation using iron(II/III) salts and ammonium hydroxide, while the second is based on a 2D material composed of MNP-decorated graphene oxide. Both MNAs were embedded in cross-linked alginate beads and used to treat artificial water contaminated with chromium(III), nickel(II), and copper(II) in different concentrations. The yield of removal and differences between MNAs and non-embedded magnetic nanomaterials are also discussed. From the results, it was found that the time to reach the adsorption equilibrium is higher when compared to that of the nanomaterials only, due to the lower surface/volume ratio of the beads, but the adsorption capacity is higher, due to the additional interaction with alginate.

Keywords:  adsorption; graphene oxide; magnetic nanoparticles; nanoadsorbents; wastewater

DOI:  https://doi.org/10.3390/ma17091942
J Hazard Mater. 2024 May 13. pii: S0304-3894(24)01177-4. [Epub ahead of print]472 134598

Exposure to 6-PPD quinone causes damage on mitochondrial complex I/II associated with lifespan reduction in Caenorhabditis elegans.

Xin Hua, Geyu Liang, Jie Chao, Dayong Wang.

  N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6-PPDQ) is an emerging pollutant transformed from 6-PPD. However, the effect of 6-PPDQ exposure on mitochondrion and underlying mechanism remains largely unclear. Using Caenorhabditis elegans as animal model, exposed to 6-PPDQ at 0.1-10 μg/L was performed form L1 larvae to adult day-1. Exposure to 6-PPDQ (1 and 10 μg/L) could increase oxygen consumption rate and decease adenosine 5'-triphosphate (ATP) content, suggesting induction of mitochondrial dysfunction. Activities of NADH dehydrogenase (complex I) and succinate dehydrogenase (complex II) were inhibited, accompanied by a decrease in expressions of gas-1, nuo-1, and mev-1. RNAi of gas-1 and mev-1 enhanced mitochondrial dysfunction and reduced lifespan of 6-PPDQ exposed nematodes. GAS-1 and MEV-1 functioned in parallel to regulate 6-PPDQ toxicity to reduce the lifespan. Insulin peptides and the insulin signaling pathway acted downstream of GAS-1 and MEV-1 to control the 6-PPDQ toxicity on longevity. Moreover, RNAi of sod-2 and sod-3, targeted genes of daf-16, caused susceptibility to 6-PPDQ toxicity in reducing lifespan and in causing reactive oxygen species (ROS) production. Therefore, 6-PPDQ at environmentally relevant concentrations (ERCs) potentially caused mitochondrial dysfunction by affecting mitochondrial complexes I and II, which was associated with lifespan reduction by affecting insulin signaling in organisms.

Keywords:  6-PPDQ; Caenorhabditis elegans; Lifespan; Mitochondrial complex; Mitochondrial dysfunction

DOI:  https://doi.org/10.1016/j.jhazmat.2024.134598
Cell Rep. 2024 May 13. pii: S2211-1247(24)00532-1. [Epub ahead of print]43(5): 114204

Rebalancing the motor circuit restores movement in a Caenorhabditis elegans model for TDP-43 toxicity.

Mandy Koopman, Lale Güngördü, Leen Janssen, Renée I Seinstra, Janet E Richmond, Nathan Okerlund, René Wardenaar, Priota Islam, Wytse Hogewerf, Andre E X Brown, Erik M Jorgensen, Ellen A A Nollen.

  Amyotrophic lateral sclerosis can be caused by abnormal accumulation of TAR DNA-binding protein 43 (TDP-43) in the cytoplasm of neurons. Here, we use a C. elegans model for TDP-43-induced toxicity to identify the biological mechanisms that lead to disease-related phenotypes. By applying deep behavioral phenotyping and subsequent dissection of the neuromuscular circuit, we show that TDP-43 worms have profound defects in GABA neurons. Moreover, acetylcholine neurons appear functionally silenced. Enhancing functional output of repressed acetylcholine neurons at the level of, among others, G-protein-coupled receptors restores neurotransmission, but inefficiently rescues locomotion. Rebalancing the excitatory-to-inhibitory ratio in the neuromuscular system by simultaneous stimulation of the affected GABA- and acetylcholine neurons, however, not only synergizes the effects of boosting individual neurotransmitter systems, but instantaneously improves movement. Our results suggest that interventions accounting for the altered connectome may be more efficient in restoring motor function than those solely focusing on diseased neuron populations.

Keywords:  C. elegans; CP: Neuroscience; G-protein coupled receptors; GABA; TDP-43; aceylcholine; amyotrophic lateral sclerosis; connectome; ion channels; neuromuscular junctions; phenomics

DOI:  https://doi.org/10.1016/j.celrep.2024.114204
J Alzheimers Dis Rep. 2024 ;8(1): 627-635

Circulating Cell Free DNA and DNA Double-Strand Breakage in Alzheimer's Disease.

Michelle Nguyen, Colby Wood, Andres Rios, Zach Salter, P Hemachandra Reddy.

  Alzheimer's disease (AD) is an age-related neurodegenerative disease that is characterized by memory loss and multiple cognitive impairments. AD is pathologically characterized by age-dependent accumulation of amyloid-β protein and the phosphorylation of tau protein in the brains of patients with AD. Clinically, manifestations of AD include cognitive decline, dementia, alterations of high-order brain functions, and movement disorders. Double-stranded DNA breaks are a lethal form of DNA damage and are typically repaired via non-homologous end joining and homologous recombination. However, in AD brain, repair mechanism is disrupted, leading to a cascade of events, cognitive dysfunction, organ failure and reduced lifespan. Increased circulating cell-free DNA in the blood, cerebrospinal fluid, and urine in patients with AD, can be used as early detectable biomarkers for AD. The purpose of our article is to explore the potential uses of cell-free DNA and double-stranded DNA breaks as prognostic markers for AD and examine the recent research on the application of these markers in studies.

Keywords:  Alzheimer’s disease; cell-free DNA; dementia; double-stranded DNA breaks

DOI:  https://doi.org/10.3233/ADR-240012
Technol Health Care. 2024 Apr 25.

An automatic measurement method for the response of Caenorhabditis elegans to chemicals.

Nan Zhang, Yanmin Nie, Bingyue Dong, Da Zhang, Guojun Li, Junyu Ning, Bo Xian, Weiyang Chen, Shan Gao.

   BACKGROUND: Caenorhabditis elegans is a widely used model animal. Chemotaxis assay is one of the experiments that study the effects of different chemicals on nematodes. It is mainly used to study the effects of different chemicals on the perception behavior of nematodes. By conducting this experiment, not only can the neurotoxicity of chemicals be reflected, but also the impact of chemicals on physiological functions regulated by the nervous system, such as nematode feeding behavior and basic motor ability.
OBJECTIVE: The experiment of detecting the response of nematode to chemicals is also a common method of chemical toxicity testing based on nematode models. In the analysis of worm tendency behavior, manual operations are generally used. Manually processing a large number of worms under a microscope is very time-consuming and labor-intensive. The current quantitative methods for nematode chemotaxis experiments are not only time-consuming and labor-intensive, but also biased in experimental results due to differences in judgment standards among experimenters. The automatic and efficient quantification method for nematode chemotaxis experiments is a very important technical difficulty in the field of nematode experiments.
METHODS: Here, we have designed an automatic quantification method for nematode chemotaxis experiments by incorporating image acquisition and processing techniques into the nematode experiment.
RESULTS: The experimental results show that the Pearson correlation coefficient between manual and automatic counting results is 0.978.
CONCLUSION: This proves the effectiveness of our method. Applying the automatic measurement method to replace manual counting by the experimenter can improve work efficiency, and reduce errors in human counting operations.

Keywords:  C. elegans; automatic quantification; behavior analysis; image processing

DOI:  https://doi.org/10.3233/THC-248013
Aging Dis. 2024 Apr 26.

Amyloid-β and Phosphorylated Tau are the Key Biomarkers and Predictors of Alzheimer's Disease.

Jangampalli Adi Pradeepkiran, Javaria Baig, Md Ariful Islam, Sudhir Kshirsagar, P Hemachandra Reddy.

Alzheimer's disease (AD) is a age-related neurodegenerative disease and is a major public health concern both in Texas, US and Worldwide. This neurodegenerative disease is mainly characterized by amyloid-beta (Aβ) and phosphorylated Tau (p-Tau) accumulation in the brains of patients with AD and increasing evidence suggests that these are key biomarkers in AD. Both Aβ and p-tau can be detected through various imaging techniques (such as positron emission tomography, PET) and cerebrospinal fluid (CSF) analysis. The presence of these biomarkers in individuals, who are asymptomatic or have mild cognitive impairment can indicate an increased risk of developing AD in the future. Furthermore, the combination of Aβ and p-tau biomarkers is often used for more accurate diagnosis and prediction of AD progression. Along with AD being a neurodegenerative disease, it is associated with other chronic conditions such as cardiovascular disease, obesity, depression, and diabetes because studies have shown that these comorbid conditions make people more vulnerable to AD. In the first part of this review, we discuss that biofluid-based biomarkers such as Aβ, p-Tau in cerebrospinal fluid (CSF) and Aβ & p-Tau in plasma could be used as an alternative sensitive technique to diagnose AD. In the second part, we discuss the underlying molecular mechanisms of chronic conditions linked with AD and how they affect the patients in clinical care.

DOI: https://doi.org/10.14336/AD.2024.0286
ACS Appl Mater Interfaces. 2024 May 15.

Multifunctional Nanocarrier for Synergistic Treatment of Alzheimer's Disease by Inhibiting β-Amyloid Aggregation and Scavenging Reactive Oxygen Species.

Chenchen Wang, Xiaolei Song, Peng Li, Shihao Sun, Juan Su, Songqin Liu, Wei Wei.

  The excessive depositions of β-amyloid (Aβ) and abnormal level of reactive oxygen species (ROS) are considered as the important pathogenic factors of Alzheimer's disease (AD). Strategies targeting only one of them have no obvious effects in clinic. In this study, a multifunctional nanocarrier CICe@M-K that crosses the blood-brain barrier (BBB) efficiently was developed for inhibiting Aβ aggregation and scavenging ROS synchronously. Antioxidant curcumin (Cur) and photosensitizer IR780 were loaded in mesoporous silica nanomaterials (MSNs). Their surfaces were grafted with cerium oxide nanoparticles (CeO2 NPs) and a short peptide K (CKLVFFAED). Living imaging showed that CICe@M-K was mainly distributed in the brain, liver, and kidneys, indicating CICe@M-K crossed BBB efficiently and accumulated in brain. After the irradiation of 808 nm laser, Cur was continuously released. Both of Cur and the peptide K can recognize and bind to Aβ through multiple interaction including π-π stacking interaction, hydrophobic interaction, and hydrogen bond, inhibiting Aβ aggregation. On the other hand, Cur and CeO2 NPs cooperate to relieve the oxidative stress in the brains by scavenging ROS. In vivo assays showed that the CICe@M-K could diminish Aβ depositions, alleviate oxidative stress, and improve cognitive ability of the APP/PS1 AD mouse model, which demonstrated that CICe@M-K is a potential agent for AD treatment.

Keywords:  Alzheimer’s disease; ROS scavenging; curcumin; synergistic treatment; β-amyloid aggregation inhibition

DOI:  https://doi.org/10.1021/acsami.4c02825
Nutr Metab (Lond). 2024 May 16. 21(1): 26

Natural products in the management of neurodegenerative diseases.

Rajat Goyal, Pooja Mittal, Rupesh K Gautam, Mohammad Amjad Kamal, Asma Perveen, Vandana Garg, Athanasios Alexiou, Muhammad Saboor, Shafiul Haque, Aisha Farhana, Marios Papadakis, Ghulam Md Ashraf.

  Neurodegenerative diseases represent one of the utmost imperative well-being health issues and apprehensions due to their escalating incidence of mortality. Natural derivatives are more efficacious in various preclinical models of neurodegenerative illnesses. These natural compounds include phytoconstituents in herbs, vegetables, fruits, nuts, and marine and freshwater flora, with remarkable efficacy in mitigating neurodegeneration and enhancing cognitive abilities in preclinical models. According to the latest research, the therapeutic activity of natural substances can be increased by adding phytoconstituents in nanocarriers such as nanoparticles, nanogels, and nanostructured lipid carriers. They can enhance the stability and specificity of the bioactive compounds to a more considerable extent. Nanotechnology can also provide targeting, enhancing their specificity to the respective site of action. In light of these findings, this article discusses the biological and therapeutic potential of natural products and their bioactive derivatives to exert neuroprotective effects and some clinical studies assessing their translational potential to treat neurodegenerative disorders.

Keywords:  Nanotechnology; Natural products; Neurodegenerative diseases; Neuroinflammation; Oxidative stress

DOI:  https://doi.org/10.1186/s12986-024-00800-4