bims-metalz Biomed News
on Metabolic causes of Alzheimer’s disease
Issue of 2023–08–20
seven papers selected by
Mikaila Chetty, Goa University



  1. Life Sci. 2023 Aug 12. pii: S0024-3205(23)00657-4. [Epub ahead of print]330 122022
      Emerging evidence have shown the importance of gut microbiota in regulating brain functions. The diverse molecular mechanisms involved in cross-talk between gut and brain provide insight into importance of this communication in maintenance of brain homeostasis. It has also been observed that disturbed gut microbiota contributes to neurological diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis and aging. Recently, gut microbiome-derived exosomes have also been reported to play an essential role in the development and progression of neurodegenerative diseases and could thereby act as a therapeutic target. Further, pharmacological interventions including antibiotics, prebiotics and probiotics can influence gut microbiome-mediated management of neurological diseases. However, extensive research is warranted to better comprehend this interconnection in maintenance of brain homeostasis and its implication in neurological diseases. Thus, the present review is aimed to provide a detailed understanding of gut-brain axis followed by possibilities to target the gut microbiome for improving neurological health.
    Keywords:  Brain; Gut; Microbiome; Neurodegeneration; Neuroinflammation
    DOI:  https://doi.org/10.1016/j.lfs.2023.122022
  2. J Biochem Mol Toxicol. 2023 Aug 18. e23485
      Gut microbiota plays a functionally important part in retaining the homeostasis of host physiology, however, under exposure of various heavy metals, the composition of gut biota is disturbed in relation to species diversity and richness. Ever since the increase of microbiome-related studies during the last decade, many research studies have delivered an understanding of the reasons and concerns of gut microbiota-related modifications. During the past decade, it's been confirmed from various studies that heavy metals poisoning alters the microbial composition, which results in changes in gene expression, alteration in metabolism, immunity, neurological dysfunction, and causes various other disorders. The present comprehensive review is summarizing an attempt to enumerate the key findings from recent clinical or preclinical studies related to the influence of heavy metals on gut microbiota published recently. Google, PubMed, Science Direct, Scopus, and Google Scholar were employed as primary search engines using the keywords such as "heavy metals, gut microbiota, dysbiosis, and intestinal microbiota" for finding relevant research articles from the past 10 years and some old important articles. Here, we tried to provide insight into some of the key timelines and scientific findings from reported literature, like the effects of heavy metals such as arsenic, cadmium, lead, and mercury on the general body and specifically on the gut microbiota of different model organisms. So, it is important to increase awareness against heavy metal-induced toxicity and formulate guidelines for the benefit of the environment.
    Keywords:  gut microbiota; heavy metals; microbial dysbiosis; microbiome
    DOI:  https://doi.org/10.1002/jbt.23485
  3. Biometals. 2023 Aug 18.
      Copper performs an important role in the brain, but in high levels it can be neurotoxic. Further, some authors have described that copper dyshomeostasis could be related with neurodegenerative diseases. Thus, this review was performed to observe whether high copper levels are related to Alzheimer's and Parkinson's diseases (AD and PD), using the literature published recently. Articles that measured copper levels in AD or PD patients was included, as well as they that measured copper levels in models used to mimic these diseases. Also, results about high copper levels effects and its relationship with AD and PD observed in laboratory animals are considered. In summary, 38 and 24 articles with AD and PD patients were included, respectively. Despite of the heterogeneity between the studies in humans, meta-analysis has demonstrated that there is an increase in free and total copper levels in the blood of AD patients compared to controls, and a decrease in copper levels in PD patients. A decrease in the metal content in postmortem brain tissue was observed in AD and PD. In manuscripts using animal models that mimic AD and PD, it was included seven and three articles, respectively. Two of them have reported an increase in copper concentrations in AD model, and one in PD model. Finally, studies with laboratory animals have concluded that high copper levels are related to oxidative stress, neuroinflammation, mitochondrial dysfunction, changes in neurotransmitter levels, cell death, and reduced both cognitive and locomotor activity, which are also described in AD or PD.
    Keywords:  Meta-analysis; Metals; Neurodegenerative diseases; Systematic review; Toxicity
    DOI:  https://doi.org/10.1007/s10534-023-00530-9
  4. Trends Cell Biol. 2023 Aug 11. pii: S0962-8924(23)00132-0. [Epub ahead of print]
      Molecules inside cells are subject to physical forces and undergo biochemical interactions, continuously changing their physical properties and dynamics. Despite this, cells achieve highly ordered molecular patterns that are crucial to regulate various cellular functions and to specify cell fate. In the Caenorhabditis elegans one-cell embryo, protein asymmetries are established in the narrow time window of a cell division. What are the mechanisms that allow molecules to establish asymmetries, defying the randomness imposed by Brownian motion? Mathematical and computational models have paved the way to the understanding of protein dynamics up to the 'single-molecule level' when resolution represents an issue for precise experimental measurements. Here we review the models that interpret cortical and cytoplasmic asymmetries in the one-cell C. elegans embryo.
    Keywords:  cortical and cytoplasmic polarity; deterministic and stochastic modelling; molecular patterning; protein dynamics; reaction–diffusion mechanisms
    DOI:  https://doi.org/10.1016/j.tcb.2023.06.009
  5. Rev Environ Health. 2023 Aug 14.
      Environmental pollution with heavy metals is widespread, thus increasing attention has been paid to their toxic effects. Recent studies have suggested that heavy metals may influence the expression of circadian clock genes. Almost all organs and tissues exhibit circadian rhythms. The normal circadian rhythm of an organism is maintained by the central and peripheral circadian clock. Thus, circadian rhythm disorders perturb normal physiological processes. Here, we review the effects of heavy metals, including manganese, copper, cadmium, and lead, on four core circadian clock genes, i.e., ARNTL, CLOCK, PER, and CRY genes.
    Keywords:  circadian clock gene; circadian rhythms; heavy metals
    DOI:  https://doi.org/10.1515/reveh-2022-0104
  6. J Fluoresc. 2023 Aug 15.
      Heavy metals such as Iron, Copper, and Zinc are micro-essential trace metal and involve animportant biological role, but it quickly turns toxic at exceeding the permissible limit, causing gastrointestinal irritation, liver, bone, and kidney damage, as well as disorders including Wilson's, Parkinson's, and Alzheimer's. It is important to detect the metal ions as well as their concentration quickly and affordable cost using organic probes. Among the organic probes,the coumarin fluorescent probe shows a very prominent candidate with heavy metal ions. Therefore, in the present review, we reviewed the very recent literature the identify the heavy metals using modified coumarin fluorescent probes. Readers will get information quickly about the method of preparation of modified coumarin core and their use as fluorescent probes with heavy metals using absorption and emission spectroscopic methods along with the probable mechanistic pathway of detection.
    Keywords:  Complexation; Copper; Coumarin; Fluorescent on-off; Fluorescent probe; Zinc
    DOI:  https://doi.org/10.1007/s10895-023-03372-3