bims-metalz Biomed News
on Metabolic causes of Alzheimer’s disease
Issue of 2023‒09‒24
eight papers selected by
Mikaila Chetty, Goa University
  1. The link between the gut microbiome, inflammation, and Parkinson's disease.
  2. Removal of extracellular human amyloid beta aggregates by extracellular proteases in C. elegans.
  3. Microbiota-Gut-Brain Axis Dysregulation in Alzheimer's Disease: Multi-Pathway Effects and Therapeutic Potential.
  4. Signaling Circuits and the Apical Extracellular Matrix In Aging: Connections Identified in the Nematode Caenorhabditis elegans.
  5. Responses of the gut microbiota to environmental heavy metal pollution in tree sparrow (Passer montanus) nestlings.
  6. Effect of dietary restriction on health span in Caenorhabditis elegans: A systematic review.
  7. Neuroactive metabolites modulated by the gut microbiota in honey bees.
  8. TGF-β pathways in aging and immunity: lessons from Caenorhabditis elegans.
  1. Appl Microbiol Biotechnol. 2023 Sep 22.
    The link between the gut microbiome, inflammation, and Parkinson's disease.
    Shiqing Nie, Yuan Ge.
      As our society ages, the growing number of people with Parkinson's disease (PD) puts tremendous pressure on our society. Currently, there is no effective treatment for PD, so there is an urgent need to find new treatment options. In recent years, increasing studies have shown a strong link between gut microbes and PD. In this review, recent advances in research on gut microbes in PD patients were summarized. Increased potential pro-inflammatory microbes and decreased potential anti-inflammatory microbes are prominent features of gut microbiota in PD patients. These changes may lead to an increase in pro-inflammatory substances (such as lipopolysaccharide and H2S) and a decrease in anti-inflammatory substances (such as short-chain fatty acids) to promote inflammation in the gut. This gut microbiota-mediated inflammation will lead to pathological α-synuclein accumulation in the gut, and the inflammation and α-synuclein can spread to the brain via the microbiota-gut-brain axis, thereby promoting neuroinflammation, apoptosis of dopaminergic neurons, and ultimately the development of PD. This review also showed that therapies based on gut microbiota may have a bright future for PD. However, more research and new approaches are still needed to clarify the causal relationship between gut microbes and PD and to determine whether therapies based on gut microbiota are effective in PD patients. KEY POINTS: • There is a strong association between gut microbes and PD. • Inflammation mediated by gut microbes may promote the development of PD. • Therapies based on the gut microbiome provide a promising strategy for PD prevention.
    Keywords:  Gut microbiome; Inflammation; Microbiota-gut-brain axis; Parkinson’s disease; Therapies based on gut microbiota
    DOI:  https://doi.org/10.1007/s00253-023-12789-6
  2. Elife. 2023 Sep 20. pii: e83465. [Epub ahead of print]12
    Removal of extracellular human amyloid beta aggregates by extracellular proteases in C. elegans.
    Elisabeth Jongsma, Anita Goyala, José Maria Mateos, Collin Yvès Ewald.
      The amyloid-beta (Aβ) plaques found in Alzheimer's disease (AD) patients' brains contain collagens and are embedded extracellularly. Several collagens have been proposed to influence Aβ aggregate formation, yet their role in clearance is unknown. To investigate the potential role of collagens in forming and clearance of extracellular aggregates in vivo, we created a transgenic Caenorhabditis elegans strain that expresses and secretes human Aβ1-42. This secreted Aβ forms aggregates in two distinct places within the extracellular matrix. In a screen for extracellular human Aβ aggregation regulators, we identified different collagens to ameliorate or potentiate Aβ aggregation. We show that a disintegrin and metalloprotease ADM-2, an orthologue of ADAM9, reduces the load of extracellular Aβ aggregates. ADM-2 is required and sufficient to remove the extracellular Aβ aggregates. Thus, we provide in-vivo evidence of collagens essential for aggregate formation and metalloprotease participating in extracellular Aβ aggregate removal.
    Keywords:  C. elegans; cell biology; neuroscience
    DOI:  https://doi.org/10.7554/eLife.83465
  3. Aging Dis. 2023 Aug 24.
    Microbiota-Gut-Brain Axis Dysregulation in Alzheimer's Disease: Multi-Pathway Effects and Therapeutic Potential.
    Linkai Qu, Yanwei Li, Fan Liu, Yimeng Fang, Jiaxuan He, Jiahui Ma, Ting Xu, Lei Wang, Pengyu Lei, Hao Dong, Libo Jin, Qinsi Yang, Wei Wu, Da Sun.
      An essential regulator of neurodegenerative conditions like Alzheimer's disease (AD) is the gut microbiota. Alterations in intestinal permeability brought on by gut microbiota dysregulation encourage neuroinflammation, central immune dysregulation, and peripheral immunological dysregulation in AD, as well as hasten aberrant protein aggregation and neuronal death in the brain. However, it is unclear how the gut microbiota transmits information to the brain and how it influences brain cognition and function. In this review, we summarized the multiple pathways involved in the gut microbiome in AD and provided detailed treatment strategies based on the gut microbiome. Based on these observations, this review also discusses the problems, challenges, and strategies to address current therapeutic strategies.
    DOI:  https://doi.org/10.14336/AD.2023.0823-2
  4. Am J Physiol Cell Physiol. 2023 Sep 18.
    Signaling Circuits and the Apical Extracellular Matrix In Aging: Connections Identified in the Nematode Caenorhabditis elegans.
    Hannah Reich, Cathy Savage-Dunn.
      Numerous conserved signaling pathways play critical roles in aging, including insulin, TGF-β, Wnt, and autophagy pathways. Some of these pathways also play prominent roles in the formation and maintenance of the extracellular matrix. The nematode Caenorhabditis elegans has been an enduringly productive system for the identification of conserved mechanisms of biological aging. Recent studies in C. elegans highlight the regulatory circuits between conserved signaling pathways and the extracellular matrix, revealing a bidirectional relationship between these factors and providing a platform to address how regulation of and by the extracellular matrix can impact lifespan and organismal health during aging. These discoveries provide new opportunities for clinical advances and novel therapeutic strategies.
    Keywords:  Caenorhabditis elegans; aging; cell signaling; cuticle; extracellular matrix
    DOI:  https://doi.org/10.1152/ajpcell.00195.2023
  5. Ecotoxicol Environ Saf. 2023 Sep 14. pii: S0147-6513(23)00984-3. [Epub ahead of print]264 115480
    Responses of the gut microbiota to environmental heavy metal pollution in tree sparrow (Passer montanus) nestlings.
    Sheng Zhang, Yue Shen, Shengnan Wang, Zhaocun Lin, Rui Su, Fei Jin, Yingmei Zhang.
      Gut microbiota plays a critical role in regulating the health and adaptation of wildlife. However, our understanding of how exposure to environmental heavy metals influences the gut microbiota of wild birds, particularly during the vulnerable and sensitive nestling stage, remains limited. In order to investigate the relationship between heavy metals and the gut microbiota, we analyzed the characteristics of gut microbiota and heavy metals levels in tree sparrow nestlings at different ages (6, 9 and 12-day-old). The study was conducted in two distinct areas: Baiyin (BY), which is heavily contaminated with heavy metals, and Liujiaxia (LJX), a relatively unpolluted area. Our result reveled a decrease in gut microbiota diversity and increased inter-individual variation among nestlings in BY. However, we also observed an increase in the abundance of bacterial groups and an up-regulation of bacterial metabolic functions associated with resistance to heavy metals toxicity in BY. Furthermore, we identified a metal-associated shift in the relative abundance of microbial taxa in 12-day-old tree sparrow nestlings in BY, particularly involving Aeromonadaceae, Ruminococcaceae and Pseudomonadaceae. Moreover, a significant positive correlation was found between the body condition of tree sparrow nestlings and the abundance of Bifidobacteriaceae in BY. Collectively, our findings indicate that the gut microbiota of tree sparrow nestlings is susceptible to heavy metals during early development. However, the results also highlight the presence of adaptive responses that enable them to effectively cope with environmental heavy metal pollution.
    Keywords:  Body condition; Diversity; Gut microbiota; Heavy metal stress; Sparrow nestling
    DOI:  https://doi.org/10.1016/j.ecoenv.2023.115480
  6. Exp Gerontol. 2023 Sep 18. pii: S0531-5565(23)00215-2. [Epub ahead of print] 112294
    Effect of dietary restriction on health span in Caenorhabditis elegans: A systematic review.
    Jazween Loo, Muhammad Arif Fikri Shah Bana, Jen Kit Tan, Jo Aan Goon.
      Dietary restriction (DR) interventions have demonstrated their efficacy in extending lifespan; however, the association between lifespan extension and health span remains unclear. This article aims to analyze the relationship between DR-induced lifespan and health span in Caenorhabditis elegans (C. elegans), a widely used animal model in lifespan studies. By examining various parameters such as lipofuscin accumulation (an aging marker) and locomotor and feeding capacities (indicators of muscle degradation rate), we have compiled papers that investigate and report on these DR-induced effects.The majority of the papers reviewed consistently demonstrate that DR improves both lifespan and health span in C. elegans. Worms subjected to DR exhibit slower lipofuscin accumulation compared to those fed ad libitum, indicating a reduction in age-related cellular damage. Additionally, DR-treated worms display a higher locomotion capacity, suggesting a slower rate of muscle degradation. However, it is worth noting that there are some discrepancies among the papers regarding feeding capacity. These contradictions can be attributed to the different methods employed to initiate DR. While many approaches slow muscle degeneration and enhance pumping rates through adaptation to limited food sources, other methods, such as using eat-2 mutant worms or interventions that mimic the effects of eat-2, reduce feeding capacity and consequently restrict food intake. In conclusion, the findings suggest a strong correlation between DR-induced longevity and the extension of health span in C. elegans, as evidenced by improvements in various health span parameters. DR interventions not only extend lifespan but also mitigate age-related markers and preserve locomotor capacity. Although conflicting results are observed regarding feeding capacity, the overall evidence supports the notion that DR promotes healthier aging in this animal model.
    Keywords:  C.elegans; Dietary restriction; Feeding; Health span; Lifespan; Lipofuscin; Movement
    DOI:  https://doi.org/10.1016/j.exger.2023.112294
  7. Mol Microbiol. 2023 Sep 17.
    Neuroactive metabolites modulated by the gut microbiota in honey bees.
    Amélie Cabirol, Silvia Moriano-Gutierrez, Philipp Engel.
      Honey bees have emerged as a new model to study the gut-brain axis, as they exhibit complex social behaviors and cognitive abilities, while experiments with gnotobiotic bees have revealed that their gut microbiota alters both brain and behavioral phenotypes. Furthermore, while honey bee brain functions supporting a broad range of behaviors have been intensively studied for over 50 years, the gut microbiota of bees has been experimentally characterized only recently. Here, we combined six published datasets from metabolomic analyses to provide an overview of the neuroactive metabolites whose abundance in the gut, hemolymph and brain varies in presence of the gut microbiota. Such metabolites may either be produced by gut bacteria, released from the pollen grains during their decomposition by bacteria, or produced by other organs in response to different bacterial products. We describe the current state of knowledge regarding the impact of such metabolites on brain function and behavior and provide further hypotheses to explore in this emerging field of research.
    Keywords:   Apis ; bacteria; behavior; brain; nutrition; symbiosis
    DOI:  https://doi.org/10.1111/mmi.15167
  8. Front Genet. 2023 ;14 1220068
    TGF-β pathways in aging and immunity: lessons from Caenorhabditis elegans.
    Katerina K Yamamoto, Cathy Savage-Dunn.
      The Transforming Growth Factor-β (TGF-β) superfamily of signaling molecules plays critical roles in development, differentiation, homeostasis, and disease. Due to the conservation of these ligands and their signaling pathways, genetic studies in invertebrate systems including the nematode Caenorhabditis elegans have been instrumental in identifying signaling mechanisms. C. elegans is also a premier organism for research in longevity and healthy aging. Here we summarize current knowledge on the roles of TGF-β signaling in aging and immunity.
    Keywords:  BMP; C. elegans; TGF-β; aging; innate immunity
    DOI:  https://doi.org/10.3389/fgene.2023.1220068
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