bims-metalz Biomed News
on Metabolic causes of Alzheimer’s disease
Issue of 2024–06–23
thirteen papers selected by
Mikaila Chetty, Goa University



  1. Am J Transl Res. 2024 ;16(5): 2011-2023
       OBJECTIVES: The increasing issue of bacterial resistance, coupled with inadequate progress in developing new antibiotics, necessitates exploring alternative treatments. Antibacterial biomaterials, such as silver and copper, possess advantageous properties such as heat resistance, durability, continuity, and safety. Particularly, they can effectively eliminate pathogenic bacteria while preserving cellular integrity, emphasizing the necessity of identifying optimal metal ion concentrations for practical application. Caenorhabditis elegans (C. elegans) can serve as a noteworthy model in this context. This study employed a C. elegans infection model to assess the efficacy of antibacterial metal ions.
    METHODS: Hematoxylin-eosin (HE) staining and inductively coupled plasma mass spectrometry (ICP-MS) assay were utilized to determine the toxic levels of metal ions in mice. Additionally, RNA sequencing (RNA-seq) and assessment of reactive oxygen species (ROS) production in the C. elegans model were conducted to elucidate the mechanisms underlying metal ion toxicity.
    RESULTS: Silver ion concentrations ranging from 10-6 to 10-7 M and copper ion concentrations ranging from 10-4 to 10-5 M exhibited antimicrobial properties without eliciting cytotoxic effects. Analysis of the transcriptome data derived from mRNA isolated from C. elegans indicated that CRKP infection activated the FoxO signaling pathway, potentially leading to ROS accumulation and C. elegans demise.
    CONCLUSIONS: In conclusion, C. elegans serves as a comprehensive infection model for assessing antibacterial metal ions.
    Keywords:  Caenorhabditis elegans; anti-infective agents; metal ion
    DOI:  https://doi.org/10.62347/DIEO8870
  2. Comp Biochem Physiol C Toxicol Pharmacol. 2024 Jun 16. pii: S1532-0456(24)00131-5. [Epub ahead of print]283 109963
      Given that Agaricus bisporus, an edible mushroom, has demonstrated antioxidant properties, our investigation aimed to assess whether Agaricus bisporus could mitigate the toxic effects of lead (Pb) on Caenorhabditis elegans (C. elegans) model. A dose-response study was conducted involving Pb and Agaricus bisporus to determine appropriate doses. Subsequently, a co-exposure study utilizing C. elegans strains N2 and CL2166 was implemented, with groups designated as Control, Pb, Agaricus bisporus, and Pb + Agaricus bisporus. Our findings revealed that co-exposure to Pb + 100 mg/mL Agaricus bisporus resulted in reduced embryonic and larval lethality, increased brood size, and enhanced motility compared to nematodes exposed solely to Pb. Notably, our observations indicated a transfer of reproductive toxicity from nematode parents to their offspring. Thus, Agaricus bisporus may play a significant role in Pb detoxification, suggesting its potential as a natural antioxidant for neutralizing the detrimental effects of Pb on reproductive health.
    Keywords:  Agaricus bisporus; Alternative animal models; Caenorhabditis elegans; Lead
    DOI:  https://doi.org/10.1016/j.cbpc.2024.109963
  3. Molecules. 2024 May 21. pii: 2428. [Epub ahead of print]29(11):
      In recent years, significant progress has been made in the subject of nanotechnology, with a range of methods developed to synthesize precise-sized and shaped nanoparticles according to particular requirements. Often, the nanoparticles are created by employing dangerous reducing chemicals to reduce metal ions into uncharged nanoparticles. Green synthesis or biological approaches have been used recently to circumvent this issue because biological techniques are simple, inexpensive, safe, clean, and extremely productive. Nowadays, much research is being conducted on how different kinds of nanoparticles connect to proteins and nucleic acids using molecular docking models. Therefore, this review discusses the most recent advancements in molecular docking capacity to predict the interactions between various nanoparticles (NPs), such as ZnO, CuO, Ag, Au, and Fe3O4, and biological macromolecules.
    Keywords:  discovery studio; green synthesis; molecular docking; nanoparticles; pymol
    DOI:  https://doi.org/10.3390/molecules29112428
  4. J Toxicol Environ Health A. 2024 Jun 21. 1-22
      Achyrocline satureioides, popularly called "marcela" in Brazil, is used in traditional medicine in South America. A. satureioides, inflorescences are used for many conditions, including to minimize the Sars-Cov-2 symptoms. Therefore, the aim of this study was to determine the toxicity profile of A. satureioides aqueous extract (ASAE), using the Caenorhabditis elegans (C. elegans) alternative model. Survival, reproduction, development, and transgenerational assays were performed. The effects of ASAE were investigated under conditions of thermal stress and presence of oxidant hydrogen peroxide (H2O2). In addition, C. elegans strains containing high antioxidant enzyme levels and elevated lineages of daf-16, skn-1 and daf-2 regulatory pathways were examined. The ASAE LC50 value was found to be 77.3 ± 4 mg/ml. The concentration of ASAE 10 mg/ml (frequently used in humans) did not exhibit a significant reduction in worm survival at either the L1 or L4 stage, after 24 or 72 hr treatment. ASAE did not markedly alter the body area. In N2 strain, ASAE (10 or 25 mg/ml) reversed the damage initiated by H2O2. In addition, ASAE protected the damage produced by H2O2 in strains containing significant levels of sod-3, gst-4 and ctl - 1,2,3, suggesting modulation in these antioxidant systems by this plant extract. ASAE exposure activated daf-16 and skn-1 stress response transcriptional pathways independently of daf-2, even under extreme stress. Data suggest that ASAE, at the concentrations tested in C. elegans, exhibits a reliable toxicity profile, which may contribute to consideration for safe use in humans.
    Keywords:  Achyrocline satureioides; Caenorhabditis elegans; gene expression; marcela; nuclear translocation; oxidative stress; toxicity
    DOI:  https://doi.org/10.1080/15287394.2024.2368618
  5. Methods Cell Biol. 2024 ;pii: S0091-679X(24)00094-3. [Epub ahead of print]188 1-34
      Caenorhabditis elegans is a nematode that has been used as an animal model for almost 50years. It has primitive and simple tissues and organs, making it an ideal model for studying neurological pathways involved in neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD). C. elegans has conserved neurological pathways and is able to mimic human diseases, providing valuable insights into the human disease phenotype. This methodological review presents current approaches to generate neurodegenerative-like models of AD and PD in C. elegans, and evaluates the experiments commonly used to validate the diseases. These experimental approaches include assessing survival, fertility, mobility, electropharyngeogram assays, confocal mitochondrial imaging, RNA extraction for qRT-PCR or RT-PCR, and rate of defecation. This review also summarizes the current knowledge acquired on AD and PD using the aforementioned experimental approaches. Additionally, gaps in knowledge and future directions for research are also discussed in the review.
    Keywords:  Animal model; Assays; Caenorhabditis elegans; Methods; Neurodegeneration; Protocols
    DOI:  https://doi.org/10.1016/bs.mcb.2024.03.004
  6. Chemistry. 2024 Jun 18. e202400277
      Amyloid plaques are a major pathological hallmark involved in Alzheimer's disease and consist of deposits of the amyloid-β peptide (Aβ). The aggregation process of Aβ is highly complex, which leads to polymorphous aggregates with different structures. In addition to aberrant aggregation, Aβ oligomers can undergo liquid-liquid phase separation and form dynamic condensates. It has been hypothesized that these amyloid liquid droplets affect and modulate amyloid fibril formation. In this review, we briefly introduce the relationship between stress granules and amyloid protein aggregation that is associated with neurodegenerative diseases. Then we highlight the regulatory role of liquid-liquid phase separation in Aβ aggregation and discuss the potential relationship between Aβ phase transition and aggregation. Furthermore, we summarize the current structures of Aβ oligomers and amyloid fibrils, which have been determined using nuclear magnetic resonance and cryo-electron microscopy. The structural variations of Aβ aggregates provide an explanation for the different levels of toxicity, shed light on the aggregation mechanism and may pave the way towards structure-based drug design for both clinical diagnosis and treatment.
    Keywords:  Alzheimer's disease; amyloid-β peptide; liquid-liquid phase separation; protein aggregation; solid-state NMR
    DOI:  https://doi.org/10.1002/chem.202400277
  7. Ageing Res Rev. 2024 Jun 18. pii: S1568-1637(24)00197-1. [Epub ahead of print] 102379
      Alzheimer's disease (AD) is a neurodegenerative disorder initiated by amyloid-beta (Aβ) accumulation, leading to impaired cognitive function. Several delivery approaches have been improved for AD management. Among them, human serum albumin (HSA) is broadly employed for drug delivery and targeting the Aβ in AD owing to its biocompatibility, Aβ inhibitory effect, and nanoform, which showed blood-brain barrier (BBB) crossing ability via glycoprotein 60 (gp60) receptor and secreted protein acidic and rich in cysteine (SPARC) protein to transfer the drug molecules in the brain. Thus far, there is no previous review focusing on HSA and its drug delivery system in AD. Hence, the reviewed article aimed to critically compile the HSA therapeutic as well as drug delivery role in AD management. It also delivers information on how HSA-incorporated nanoparticles with surfaced embedded ligands such as TAT, GM1, and so on, not only improve BBB permeability but also increase neuron cell targetability in AD brain. Additionally, Aβ and tau pathology, including various metabolic markers likely BACE1 and BACE2, etc., are discussed. Besides, the molecular interaction of HSA with Aβ and its distinctive forms are critically reviewed that HSA can segregate Zn(II) and Cu(II) metal ions from Aβ owing to high affinity. Furthermore, the BBB drug delivery challenges in AD are addressed. Finally, the clinical formulation of HSA for the management of AD is critically discussed on how the HSA inhibits Aβ oligomer and fibril, while glycated HSA participates in amyloid plaque formation, i.e., β-structure sheet formation. This review report provides theoretical background on HSA-based AD drug delivery and makes suggestions for future prospect-related work.
    Keywords:  Alzheimer's disease (AD); beta-amyloid and tau; drug delivery and nanomedicine; human serum albumin (HSA) and its modifications; preclinical and clinical role of HSA
    DOI:  https://doi.org/10.1016/j.arr.2024.102379
  8. J Pharm Bioallied Sci. 2024 Apr;16(Suppl 2): S1211-S1216
      Solanum trilobatum L. (Solanaceae), commonly known as nightshade, has been traditionally used by various populations to treat a variety of ailments. Environment-friendly alternatives to chemical and physical procedures for the synthesis of nanomaterials have been proposed. In this research, the hot plate combustion method is used to synthesize nickel oxide nanoparticles (AgNPs) from silver nitrate and S. trilobatum leaf extract. According to X-ray diffraction (XRD) tests, the cubic phase was face-centered, had good crystallinity, and had average crystallite sizes. According to morphological studies, the surface has a cylindrical and rod-like morphology, and average particle size estimates from UV-visible spectroscopy (UV), Fourier transform infrared (FT-IR), concur well with XRD, and the bio-reduced silver nanoparticles were characterized. Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans, Pseudomonas aeruginosa, and the human pathogenic microorganisms were used to investigate the antibacterial efficacy (12.5, 25, 50 μg/mL) of these biologically created silver nanoparticles.
    Keywords:  FTIR; SEM; Solanum trilobatum; UV; good health and well-being; industry innovation and infrastructure and antibacterial; sustainable innovation
    DOI:  https://doi.org/10.4103/jpbs.jpbs_544_23
  9. Pharm Nanotechnol. 2024 Jun 11.
       BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and is expected to greatly rise in future, making it a major worldwide health concern with severe impacts on individuals and society. Despite advancements in understanding the cellular and molecular aspects of Alzheimer's disease (AD) in recent decades, it still poses a significant problem. A major problem is accurately delivering drugs to diseased neurons while minimising effects on healthy neurons. This difficulty is worsened by the low water solubility of anti-Alzheimer's disease medicines and the blood-brain barrier (BBB) that hinders the entry of central nervous system pharmaceuticals that are highly lipophilic.
    OBJECTIVE: The focus of this article is on nanocarriers that are lipid-based. This is one of the more widely accepted methods of treating Alzheimer's disease, as it increases therapeutic efficacy while decreasing side effects related to cooperated neurological disorder payload.
    METHOD: Searched many databases for papers published under the title (including PubMed, Elsevier, and Google Scholar).
    RESULTS/CONCLUSION: Nano Lipid Carriers (NLCs) are recognized for their ability to target the brain effectively due to their lipid-loving properties and compatibility with living tissues. They improve the absorption of drugs in the brain while decreasing the accumulation of drugs in unintended organs. This work emphasises the importance of nano lipid carriers, which are lipophilic and biocompatible and have demonstrated exceptional targeting efficiency, making them an ideal carrier system for delivering medications to the brain.
    Keywords:  Alzheimer's; CNS; Nanomedicine; blood-brain barrier.; lipid-based approaches; nano lipid carriers; nanoparticles
    DOI:  https://doi.org/10.2174/0122117385300234240522100826
  10. Foods. 2024 May 30. pii: 1716. [Epub ahead of print]13(11):
      Sorghum grain contains high levels and a diverse profile of polyphenols (PPs), which are antioxidants known to reduce oxidative stress when consumed in the diet. Oxidative stress leading to amyloid-β (Aβ) aggregation, neurotoxicity, and mitochondrial dysfunction is implicated in the pathogenesis of Alzheimer's disease (AD). Thus, PPs have gained attention as possible therapeutic agents for combating AD. This study aimed to (a) quantify the phenolic compounds (PP) and antioxidant capacities in extracts from six different varieties of sorghum grain and (b) investigate whether these PP extracts exhibit any protective effects on human neuroblastoma (BE(2)-M17) cells against Aβ- and tau-induced toxicity, Aβ aggregation, mitochondrial dysfunction, and reactive oxygen species (ROS) induced by Aβ and tert-butyl hydroperoxide (TBHP). PP and antioxidant capacity were quantified using chemical assays. Aβ- and tau-induced toxicity was determined using the 3-(4,5-dimenthylthiazol-2-yl)-2,5-dimethyltetrazolium bromide (MTS) assay. The thioflavin T (Th-T) assay assessed anti-Aβ aggregation. The dichlorodihydrofluorescein diacetate (DCFDA) assay determined the levels of general ROS and the MitoSOX assay determined the levels of mitochondrial superoxide. Sorghum varieties Shawaya short black-1 and IS1311C possessed the highest levels of total phenolics, total flavonoids, and antioxidant capacity, and sorghum varieties differed significantly in their profile of individual PPs. All extracts significantly increased cell viability compared to the control (minus extract). Variety QL33 (at 2000 µg sorghum flour equivalents/mL) showed the strongest protective effect with a 28% reduction in Aβ-toxicity cell death. The extracts of all sorghum varieties significantly reduced Aβ aggregation. All extracts except that from variety B923296 demonstrated a significant (p ≤ 0.05) downregulation of Aβ-induced and TBHP-induced ROS and mitochondrial superoxide relative to the control (minus extract) in a dose- and variety-dependent manner. We have demonstrated for the first time that sorghum polyphenolic extracts show promising neuroprotective effects against AD, which indicates the potential of sorghum foods to exert a similar beneficial property in the human diet. However, further analysis in other cellular models and in vivo is needed to confirm these effects.
    Keywords:  Alzheimer’s disease; amyloid-β; antioxidants; mitochondrial function; neuroprotection; polyphenols; reactive oxygen species; sorghum
    DOI:  https://doi.org/10.3390/foods13111716
  11. Cureus. 2024 May;16(5): e60407
       BACKGROUND: Nanotechnology enables precise manipulation of matter at the molecular level, with nanoparticles offering diverse applications in medicine and beyond. Green synthesis methods, utilizing natural sources like plant extracts, are favored for their eco-friendliness. Zinc oxide (ZnO) nanoparticles are recognized for their ability to combat microbes and reduce inflammation, which holds promise for biomedical applications. Catharanthus roseus, renowned for its medicinal properties, warrants further exploration in oral health management due to its anti-inflammatory and antioxidant attributes.
    AIM: The current study aimed to synthesize Catharanthus roseus-mediated ZnO nanoparticles and to evaluate their anti-inflammatory and antioxidant activity.
    MATERIALS AND METHODS: Catharanthus roseus powder (1 g) was dissolved in distilled water (100 ml), heated at 60°C for 15-20 minutes, and filtered to obtain 20 ml extract. ZnO nanoparticles were synthesized by adding 0.594 g ZnO powder to 50 ml water, mixed with plant extract, and stirred for 72 hours, and the resulting solution was centrifuged. Nanoparticles were collected and analyzed for Fourier-transform infrared spectroscopy (FTIR) using Bruker's Alpha II FTIR spectrometer (Bruker, Billerica, Massachusetts, United States), antioxidant, and anti-inflammatory activities.
    RESULTS: FTIR analysis revealed characteristic peaks indicative of functional groups present in Catharanthus roseus-mediated ZnO nanoparticles, including O-H, N-O, C-O, C=C, and C≡C-H. Anti-inflammatory activity evaluation showed inhibition ranging from 48% to 89%, with the maximum inhibition at 50 μL concentration. Similarly, antioxidant activity ranged from 62% to 88%, with the maximum inhibition also seen at 50 μL concentration.
    CONCLUSION: Both assays effectively showcased the superior anti-inflammatory and antioxidant activity of the Catharanthus roseus-incorporated ZnO nanoparticles extract compared to the control. This suggests their potential as a viable therapeutic agent for further evaluation.
    Keywords:  anti-inflammatory; anti-oxidant; catharanthus roseus; green synthesis; zinc oxide nanoparticles
    DOI:  https://doi.org/10.7759/cureus.60407
  12. Mar Environ Res. 2024 Jun 14. pii: S0141-1136(24)00256-3. [Epub ahead of print]199 106595
      A massive fish mortality of the major species, viz., Mugil cephalus, Chanos chanos, and Oreochromis mossambicus, occurred on November 27, 2017 in the Adyar estuary. This catastrophe followed a spell of heavy rainfall and flash floods. A detailed study of water quality parameters (pH, water temperature, salinity, total suspended matter, dissolved oxygen, biochemical oxygen demand, and nutrients) and heavy metals, i.e., chromium (Cr), copper (Cu), cadmium (Cd), nickel (Ni), lead (Pb), and zinc (Zn), in the sediment and fish tissues were analyzed. Pollution indices like the enrichment factor (EF), geo-accumulation index (Igeo), contamination factor (CF), pollution load index (PLI), potential ecological risk index (PERI), and biota sediment accumulation factor (BSAF) were used to measure heavy metals. The pollution indices revealed that metals were significantly enriched in the sediments. The Igeo indicates that there was moderate contamination by Cd (2.27-3.25), whereas CF shows high contamination by Cd (7.22-9.72) and moderate contamination by Pb (2.5-3.25). The PLI (1.04-1.13) suggests that heavy metal contamination of sediments has occurred. Results showed that high concentrations of the toxic metals Pb and Cd were found in the sediment as well as in fish tissues. Length and weight of fish are significantly correlated (r2 = 0.98, p < 0.05). The study revealed that the mass fish kill was due to impulsive changes in the water quality and heavy metal pollution from untreated urban sewage discharges in this region.
    Keywords:  Chennai coast; Fish mortality; Heavy metals toxicity; Pollution indices; Tropical estuary
    DOI:  https://doi.org/10.1016/j.marenvres.2024.106595