bims-metalz Biomed News
on Metabolic causes of Alzheimer’s disease
Issue of 2023–12–10
three papers selected by
Mikaila Chetty, Goa University



  1. Ecotoxicol Environ Saf. 2023 Dec 05. pii: S0147-6513(23)01242-3. [Epub ahead of print]269 115738
      Studies have probed nanoplastic toxicity on environmental organisms, but the regulatory role of animal PIEZO-type mechanosensitive ion channel component (PIEZO) remains unclear. Herein, we identified the sole PIEZO in Caenorhabditis elegans (C. elegans), utilizing amino acid homology analysis and Trans-Membrane prediction using Hidden Markov Models (TMHMM). In C. elegans, RNAi knockdown of pezo-1 had no impact on lifespan, body length, lethality, locomotion behaviors, or oxidative response (P > 0.05). However, exposure to 15 μg/L nanopolystyrene in the pezo-1 RNAi group resulted in severe locomotion changes: head trashes (P < 0.01), body bends (P < 0.05), forward turns (P < 0.05), backward turns (P < 0.01), and impaired sensory perception, including abnormal chemotaxis to NaCl (P < 0.01) and diacetyl (P < 0.01), as well as aversive responses (P < 0.05) to nanopolystyrene compared to the wild-type group. Dopaminergic neuron damage explains these behaviors, with GST-4 (P < 0.01) and SKN-1/Nrf2 (P < 0.01) activation mitigating nanoplastic-induced damage. Our results emphasize that even at the environmentally relevant concentrations (ERC), nanoplastics can impact neurotoxicity-related endpoints, with PIEZO mediating the regulation of oxidative and antioxidative systems in response to these effects. PIEZO may be applied for assessing the neurotoxicity or oxidative stress induced by other environmental toxicants besides nanoplastics.
    Keywords:  Caenorhabditis elegans; ERC; Nanoplastics; Neurotoxicity; PIEZO
    DOI:  https://doi.org/10.1016/j.ecoenv.2023.115738
  2. Aging Cell. 2023 Dec 03. e14055
      The heterogeneity of aging has been investigated at cellular and organic levels in the mouse model and human, but the exploration of aging heterogeneity at whole-organism level is lacking. C. elegans is an ideal model organism for studying this question as they are self-fertilized and cultured in the same chamber. Despite the tremendous progress made in single-cell proteomic analysis, there is few single-worm proteomics studies about aging. Here, we apply single-worm quantitative mass spectrometry to quantify the heterogenous proteomic changes during aging across individuals, a total of 3524 proteins from 157 C. eleagns individuals were quantified. A reconstructed C. elegans aging trajectory and proteomic landscape of fast-aging individuals were used to analyze the heterogeneity of C. elegans aging. We characterized inter-individual proteomic variation during aging and revealed contributing factors that distinguish fast-aging individuals from their siblings.
    Keywords:  aging; mass spectrometry; single worm proteomics
    DOI:  https://doi.org/10.1111/acel.14055
  3. Comput Struct Biotechnol J. 2023 ;21 5662-5675
      Alzheimer's disease (AD) is the most common form of dementia. Unfortunately, despite numerous studies, an effective treatment for AD has not yet been established. There is remarkable evidence indicating that the innate immune mechanism and adaptive immune response play significant roles in the pathogenesis of AD. Several studies have reported changes in CD8+ and CD4+ T cells in AD patients. This mini-review article discusses the potential contribution of CD4+ and CD8+ T cells reactivity to amyloid β (Aβ) protein in individuals with AD. Moreover, this mini-review examines the potential associations between T cells, heme oxygenase (HO), and impaired mitochondria in the context of AD. While current mathematical models of AD have not extensively addressed the inclusion of CD4+ and CD8+ T cells, there exist models that can be extended to consider AD as an autoimmune disease involving these T cell types. Additionally, the mini-review covers recent research that has investigated the utilization of machine learning models, considering the impact of CD4+ and CD8+ T cells.
    Keywords:  Alzheimer's disease; Amyloid β-protein; CD4+ T cells; CD8+ T cells; Cytokines; Machine learning; Tregs
    DOI:  https://doi.org/10.1016/j.csbj.2023.10.058