bims-metalz Biomed News
on Metabolic causes of Alzheimer’s disease
Issue of 2024‒02‒25
six papers selected by
Mikaila Chetty, Goa University
  1. Butein Increases Resistance to Oxidative Stress and Lifespan with Positive Effects on the Risk of Age-Related Diseases in Caenorhabditis elegans.
  2. Dysfunction in atox-1 and ceruloplasmin alters labile Cu levels and consequently Cu homeostasis in C. elegans.
  3. N-3 polyunsaturated fatty acids attenuate amyloid-beta-induced toxicity in AD transgenic Caenorhabditis elegans via promotion of proteasomal activity and activation of PPAR-gamma.
  4. Lipid-Lowering and Antioxidant Effects of Self-Assembled Astaxanthin-Anthocyanin Nanoparticles on High-Fat Caenorhabditis elegans.
  5. Dendrobium Nobile Alcohol Extract Extends the Lifespan of Caenorhabditis elegans via hsf-1 and daf-16.
  6. Toxicity of representative organophosphate, organochlorine, phenylurea, dinitroaniline, carbamate, and viologen pesticides to the growth and survival of H. vulgaris, L. minor, and C. elegans.
  1. Antioxidants (Basel). 2024 Jan 26. pii: 155. [Epub ahead of print]13(2):
    Butein Increases Resistance to Oxidative Stress and Lifespan with Positive Effects on the Risk of Age-Related Diseases in Caenorhabditis elegans.
    Seona Kim, Hyemin Yoon, Sang-Kyu Park.
      Butein is a flavonoid found in many plants, including dahlia, butea, and coreopsis, and has both antioxidant and sirtuin-activating activities. In light of the postulated role of free radicals in aging, we examined the effects of butein on aging and on genetic or nutritional models of age-related diseases in Caenorhabditis elegans. Butein showed radical scavenging activity and increased resistance to oxidative stress in Caenorhabditis elegans. The mean lifespan of Caenorhabditis elegans was significantly increased by butein, from 22.7 days in the untreated control to 25.0 days in the butein-treated group. However, the lifespan-extending effect of butein was accompanied by reduced production of progeny as a trade-off. Moreover, the age-related decline in motility was delayed by butein supplementation. Genetic analysis showed that the lifespan-extending effect of butein required the autophagic protein BEC-1 and the transcription factor DAF-16 to regulate stress response and aging. At the genetic level, expression of the DAF-16 downstream target genes hsp-16.2 and sod-3 was induced in butein-treated worms. Butein additionally exhibited a preventive effect in models of age-related diseases. In an Alzheimer's disease model, butein treatment significantly delayed the paralysis caused by accumulation of amyloid-beta in muscle, which requires SKN-1, not DAF-16. In a high-glucose-diet model of diabetes mellitus, butein markedly improved survival, requiring both SKN-1 and DAF-16. In a Parkinson's disease model, dopaminergic neurodegeneration was completely inhibited by butein supplementation and the accumulation of α-synuclein was significantly reduced. These findings suggest the use of butein as a novel nutraceutical compound for aging and age-related diseases.
    Keywords:  C. elegans; age-related diseases; butein; lifespan; oxidative stress
    DOI:  https://doi.org/10.3390/antiox13020155
  2. Front Mol Biosci. 2024 ;11 1354627
    Dysfunction in atox-1 and ceruloplasmin alters labile Cu levels and consequently Cu homeostasis in C. elegans.
    Ann-Kathrin Weishaupt, Karsten Lamann, Elke Tallarek, Aidan T Pezacki, Carson D Matier, Tanja Schwerdtle, Michael Aschner, Christopher J Chang, Stephen R Stürzenbaum, Julia Bornhorst.
      Copper (Cu) is an essential trace element, however an excess is toxic due to its redox properties. Cu homeostasis therefore needs to be tightly regulated via cellular transporters, storage proteins and exporters. An imbalance in Cu homeostasis has been associated with neurodegenerative disorders such as Wilson's disease, but also Alzheimer's or Parkinson's disease. In our current study, we explored the utility of using Caenorhabditis elegans (C. elegans) as a model of Cu dyshomeostasis. The application of excess Cu dosing and the use of mutants lacking the intracellular Cu chaperone atox-1 and major Cu storage protein ceruloplasmin facilitated the assessment of Cu status, functional markers including total Cu levels, labile Cu levels, Cu distribution and the gene expression of homeostasis-related genes. Our data revealed a decrease in total Cu uptake but an increase in labile Cu levels due to genetic dysfunction, as well as altered gene expression levels of Cu homeostasis-associated genes. In addition, the data uncovered the role ceruloplasmin and atox-1 play in the worm's Cu homeostasis. This study provides insights into suitable functional Cu markers and Cu homeostasis in C. elegans, with a focus on labile Cu levels, a promising marker of Cu dysregulation during disease progression.
    Keywords:  C. elegans; ToF-SIMS; copper; homeostasis; total vs. labile copper
    DOI:  https://doi.org/10.3389/fmolb.2024.1354627
  3. J Nutr Biochem. 2024 Feb 17. pii: S0955-2863(24)00036-6. [Epub ahead of print] 109603
    N-3 polyunsaturated fatty acids attenuate amyloid-beta-induced toxicity in AD transgenic Caenorhabditis elegans via promotion of proteasomal activity and activation of PPAR-gamma.
    Yanqing Wang, Huanying Zhang, Feng Ding, Jianhua Li, Lianyu Li, Zhong Xu, Yan Zhao.
      Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. A major pathological characteristic of AD brain is the presence of senile plaques composed of β-amyloid (Aβ), the accumulation of which induces toxic cascades leading to synaptic dysfunction, neuronal apoptosis and eventually cognitive decline. Dietary n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial for patients with early stage of AD; however, the mechanisms are not completely understood. In this study, we investigated the effects of n-3 PUFAs on Aβ-induced toxicity in a transgenic AD Caenorhabditis elegans (C. elegans) model. The results showed that EPA and DHA significantly inhibited Aβ-induced paralytic phenotype and decreased the production of reactive oxygen species while reducing the levels of Aβ in the AD worms. Further studies revealed that EPA and DHA might reduce the accumulation of Aβ by restoring the activity of proteasome. Moreover, treating worms with peroxisome proliferator activated receptor (PPAR)-γ inhibitor GW9662 prevented the inhibitory effects of n-3 PUFAs on Aβ-induced paralytic phenotype and diminished the elevation of proteasomal activity by n-3 PUFAs, suggesting that PPARγ-mediated signals play important role in the protective effects of n-3 PUFAs against Aβ-induced toxicity.
    Keywords:  Alzheimer's disease; Aβ; N-3 PUFAs; PPARγ; proteasomal activity
    DOI:  https://doi.org/10.1016/j.jnutbio.2024.109603
  4. Foods. 2024 Feb 07. pii: 514. [Epub ahead of print]13(4):
    Lipid-Lowering and Antioxidant Effects of Self-Assembled Astaxanthin-Anthocyanin Nanoparticles on High-Fat Caenorhabditis elegans.
    Deyang Yu, Meng Guo, Mingqian Tan, Wentao Su.
      Obesity has become a serious global public health risk threatening millions of people. In this study, the astaxanthin-anthocyanin nanoparticles (AXT-ACN NPs) were used to investigate their effects on the lipid accumulation and antioxidative capacity of the high-sugar-diet-induced high-fat Caenorhabditis elegans (C. elegans). It can be found that the lifespan, motility, and reproductive capacity of the high-fat C. elegans were significantly decreased compared to the normal nematodes in the control group. However, treatment of high-fat C. elegans with AXT-ACN NPs resulted in a prolonged lifespan of 35 days, improved motility, and a 22.06% increase in total spawn production of the nematodes. Furthermore, AXT-ACN NPs were found to effectively extend the lifespan of high-fat C. elegans under heat and oxidative stress conditions. Oil-red O staining results also demonstrated that AXT-ACN NPs have a remarkable effect on reducing the fat accumulation in nematodes, compared with pure astaxanthin and anthocyanin nanoparticles. Additionally, AXT-ACN NPs can significantly decrease the accumulation of lipofuscin and the level of reactive oxygen species (ROS). The activities of antioxidant-related enzymes in nematodes were further measured, which revealed that the AXT-ACN NPs could increase the activities of catalase (CAT), superoxidase dismutase (SOD), and glutathione peroxidase (GSH-Px), and decrease the malondialdehyde (MDA) content. The astaxanthin and anthocyanin in AXT-ACN NPs showed sound synergistic antioxidation and lipid-lowering effects, making them potential components in functional foods.
    Keywords:  Caenorhabditis elegans; Mannich reaction; anthocyanin; antioxidant; astaxanthin; high-fat diet; lipid-lowering; microfluidic chip
    DOI:  https://doi.org/10.3390/foods13040514
  5. Molecules. 2024 Feb 19. pii: 908. [Epub ahead of print]29(4):
    Dendrobium Nobile Alcohol Extract Extends the Lifespan of Caenorhabditis elegans via hsf-1 and daf-16.
    Linfeng Li, Zhen Liu, Huiling Hu, Renming Cai, Jingdou Bi, Qin Wang, Xiaogang Zhou, Huairong Luo, Chun Zhang, Runlan Wan.
      Dendrobium nobile is a traditional Chinese herb with anti-inflammatory, antioxidant, and neuroprotective properties. However, its antiaging effects are unclear. Herein, we studied the aging-related functions and the mechanism of action of the alcohol extract of Dendrobium nobile (DnAE) in the model organism Caenorhabditis elegans. The results indicated that 1 mg/mL DnAE slowed lipofuscin accumulation, decreased the levels of reactive oxygen species, elevated superoxide dismutase activity, enhanced oxidative and heat stress resistance, extended the lifespan of nematodes, protected their dopamine neurons from 6-hydroxydopamine-induced neurodegeneration, and reduced Aβ-induced neurotoxicity. DnAE upregulated the mRNA expression of the transcription factors DAF-16 and HSF-1, promoted the nuclear localization of DAF-16, and enhanced the fluorescence intensity of HSP-16.2. However, it had no effect on the lifespan of DAF-16 mutants. Thus, DnAE can significantly extend lifespan, enhance heat stress tolerance, and delay age-related diseases through a DAF-16-dependent pathway.
    Keywords:  Caenorhabditis elegans; DAF-16; alzheimer’s disease; antiaging; dendrobium nobile; parkinson’s disease
    DOI:  https://doi.org/10.3390/molecules29040908
  6. Environ Sci Pollut Res Int. 2024 Feb 24.
    Toxicity of representative organophosphate, organochlorine, phenylurea, dinitroaniline, carbamate, and viologen pesticides to the growth and survival of H. vulgaris, L. minor, and C. elegans.
    Kelly J Rivenbark, Hasan Nikkhah, Meichen Wang, Burcu Beykal, Timothy D Phillips.
      Pesticides are commonly found in the environment and pose a risk to target and non-target species; therefore, employing a set of bioassays to rapidly assess the toxicity of these chemicals to diverse species is crucial. The toxicity of nine individual pesticides from organophosphate, organochlorine, phenylurea, dinitroaniline, carbamate, and viologen chemical classes and a mixture of all the compounds were tested in three bioassays (Hydra vulgaris, Lemna minor, and Caenorhabditis elegans) that represent plant, aquatic, and soil-dwelling species, respectively. Multiple endpoints related to growth and survival were measured for each model, and EC10 and EC50 values were derived for each endpoint to identify sensitivity patterns according to chemical classes and target organisms. L. minor had the lowest EC10 and EC50 values for seven and five of the individual pesticides, respectively. L. minor was also one to two orders of magnitude more sensitive to the mixture compared to H. vulgaris and C. elegans, where EC50 values were calculated to be 0.00042, 0.0014, and 0.038 mM, respectively. H. vulgaris was the most sensitive species to the remaining individual pesticides, and C. elegans consistently ranked the least sensitive to all tested compounds. When comparing the EC50 values across all pesticides, the endpoints of L. minor were correlated with each other while the endpoints measured in H. vulgaris and C. elegans were clustered together. While there was no apparent relationship between the chemical class of pesticide and toxicity, the compounds were more closely clustered based on target organisms (herbicide vs insecticide). The results of this study demonstrate that the combination of these plant, soil, and aquatic specie can serve as representative indicators of pesticide pollution in environmental samples.
    Keywords:  Battery of bioassays; EC10; EC50; Ecotoxicology; Herbicides; Insecticides
    DOI:  https://doi.org/10.1007/s11356-024-32444-5
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