bims-metalz Biomed News
on Metabolic causes of Alzheimer’s disease
Issue of 2024–01–14
seven papers selected by
Mikaila Chetty, Goa University
  1. Towards Understanding Neurodegenerative Diseases: Insights from Caenorhabditis elegans.
  2. Amyotrophic Lateral Sclerosis Mechanism: Insights from the Caenorhabditis elegans Models.
  3. Icariin Improves Stress Resistance and Extends Lifespan in Caenorhabditis elegans through hsf-1 and daf-2-Driven Hormesis.
  4. The mechanoreceptor pezo-1 is required for normal crawling locomotion in the nematode C. elegans.
  5. Anti-Aging Effect of Hemerocallis citrina Baroni Polysaccharide-Rich Extract on Caenorhabditis elegans.
  6. Nanotechnology in the diagnostic and therapy for Alzheimer's disease.
  7. A full-body transcription factor expression atlas with completely resolved cell identities in C. elegans.
  1. Int J Mol Sci. 2023 Dec 28. pii: 443. [Epub ahead of print]25(1):
    Towards Understanding Neurodegenerative Diseases: Insights from Caenorhabditis elegans.
    Yingjie Wu, Yining Chen, Xiaochun Yu, Minxing Zhang, Zhaoyu Li.
      The elevated occurrence of debilitating neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD) and Machado-Joseph disease (MJD), demands urgent disease-modifying therapeutics. Owing to the evolutionarily conserved molecular signalling pathways with mammalian species and facile genetic manipulation, the nematode Caenorhabditis elegans (C. elegans) emerges as a powerful and manipulative model system for mechanistic insights into neurodegenerative diseases. Herein, we review several representative C. elegans models established for five common neurodegenerative diseases, which closely simulate disease phenotypes specifically in the gain-of-function aspect. We exemplify applications of high-throughput genetic and drug screenings to illustrate the potential of C. elegans to probe novel therapeutic targets. This review highlights the utility of C. elegans as a comprehensive and versatile platform for the dissection of neurodegenerative diseases at the molecular level.
    Keywords:  C. elegans; C9ORF72; FUS; SOD1; TDP-43; amyloid β1-42; gain-of-toxicity; polyQ; tau; α-synuclein
    DOI:  https://doi.org/10.3390/ijms25010443
  2. Cells. 2024 Jan 03. pii: 99. [Epub ahead of print]13(1):
    Amyotrophic Lateral Sclerosis Mechanism: Insights from the Caenorhabditis elegans Models.
    Lili Chen, Shumei Zhang, Sai Liu, Shangbang Gao.
      Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative condition characterized by the progressive degeneration of motor neurons. Despite extensive research in various model animals, the cellular signal mechanisms of ALS remain elusive, impeding the development of efficacious treatments. Among these models, a well-characterized and diminutive organism, Caenorhabditis elegans (C. elegans), has emerged as a potent tool for investigating the molecular and cellular dimensions of ALS pathogenesis. This review summarizes the contributions of C. elegans models to our comprehension of ALS, emphasizing pivotal findings pertaining to genetics, protein aggregation, cellular pathways, and potential therapeutic strategies. We analyze both the merits and constraints of the C. elegans system in the realm of ALS research and point towards future investigations that could bridge the chasm between C. elegans foundational discoveries and clinical applications.
    Keywords:  ALS; C. elegans model; cellular mechanism; therapeutic application
    DOI:  https://doi.org/10.3390/cells13010099
  3. Int J Mol Sci. 2023 Dec 26. pii: 352. [Epub ahead of print]25(1):
    Icariin Improves Stress Resistance and Extends Lifespan in Caenorhabditis elegans through hsf-1 and daf-2-Driven Hormesis.
    Monika N Todorova, Martina S Savova, Liliya V Mihaylova, Milen I Georgiev.
      Aging presents an increasingly significant challenge globally, driven by the growing proportion of individuals aged 60 and older. Currently, there is substantial research interest in pro-longevity interventions that target pivotal signaling pathways, aiming not only to extend lifespan but also to enhance healthspan. One particularly promising approach involves inducing a hormetic response through the utilization of natural compounds defined as hormetins. Various studies have introduced the flavonoid icariin as beneficial for age-related diseases such as cardiovascular and neurodegenerative conditions. To validate its potential pro-longevity properties, we employed Caenorhabditis elegans as an experimental platform. The accumulated results suggest that icariin extends the lifespan of C. elegans through modulation of the DAF-2, corresponding to the insulin/IGF-1 signaling pathway in humans. Additionally, we identified increased resistance to heat and oxidative stress, modulation of lipid metabolism, improved late-life healthspan, and an extended lifespan upon icariin treatment. Consequently, a model mechanism of action was provided for icariin that involves the modulation of various players within the stress-response network. Collectively, the obtained data reveal that icariin is a potential hormetic agent with geroprotective properties that merits future developments.
    Keywords:  Caenorhabditis elegans; aging; healthspan; icariin; lifespan; longevity
    DOI:  https://doi.org/10.3390/ijms25010352
  4. MicroPubl Biol. 2023 ;2023
    The mechanoreceptor pezo-1 is required for normal crawling locomotion in the nematode C. elegans.
    Adithya Komandur, Adina Fazyl, Wolfgang Stein, Andrés G Vidal-Gadea.
      The discovery in 2010 of the PIEZO family of mechanoreceptors revolutionized our understanding of the role of proprioceptive feedback in mammalian physiology. Much remains to be elucidated. This study looks at the role this receptor plays in normal locomotion. Like humans, the nematode C. elegans expresses PIEZO-type channels (encoded by the pezo-1 gene) throughout its somatic musculature. Here we use the unbiased automated behavioral software Tierpsy to characterize the effects that mutations removing PEZO-1 from body wall musculature have on C. elegans crawling. We find that loss of PEZO-1 results in disrupted locomotion and posture, consistent with phenotypes associated with loss of PIEZO2 in human musculature. C. elegans is thus an amenable system to study the role of mechanoreception on muscle physiology and function.
    DOI:  https://doi.org/10.17912/micropub.biology.001085
  5. Int J Mol Sci. 2024 Jan 04. pii: 655. [Epub ahead of print]25(1):
    Anti-Aging Effect of Hemerocallis citrina Baroni Polysaccharide-Rich Extract on Caenorhabditis elegans.
    Yunxia Zou, Xiyue Qin, Wenli Wang, Qingyong Meng, Yali Zhang.
      Plant polysaccharides are important for anti-aging research. Polysaccharides from Hemerocallis citrina Baroni (H. citrina) have been reported to have antioxidant activity; however, their anti-aging roles and mechanisms are not clear. In this study, we extracted polysaccharides from H. citrina by an ultrasonic-assisted water extraction-alcohol precipitation method and chemically determined the physicochemical properties such as extraction yield, content, and in vitro antioxidant properties of H. citrina polysaccharide-rich extract (HCPRE). Using Caenorhabditis elegans (C. elegans) as a model animal, the anti-aging effect of HCPRE was investigated, and the mechanism of action of HCPRE was explored by the in vivo antioxidant level assay of C. elegans and the related gene expression assay. The extraction yield of HCPRE was 11.26%, the total polysaccharide content was 77.96%, and the main monosaccharide components were glucose and galactose. In addition, HCPRE exhibited good antioxidant activity both in vitro and in vivo. Under normal thermal stress and oxidative stress conditions, being fed 1200 µg/mL of HCPRE significantly prolonged the life span of C. elegans by 32.65%, 17.71%, and 32.59%, respectively. Our study showed that HCPRE exerted an anti-aging effect on C. elegans, and its mechanism involves increasing the activities of catalase (CAT) and superoxide dismutase (SOD), reducing the level of reactive oxygen species (ROS) and regulating the expression of related genes.
    Keywords:  C. elegans; Hemerocallis citrina Baroni; antioxidant; longevity; polysaccharide
    DOI:  https://doi.org/10.3390/ijms25010655
  6. Biochim Biophys Acta Gen Subj. 2024 Jan 06. pii: S0304-4165(24)00002-3. [Epub ahead of print]1868(3): 130559
    Nanotechnology in the diagnostic and therapy for Alzheimer's disease.
    Archna Panghal, S J S Flora.
      Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by β-amyloid plaque, intraneuronal tangles, significant neuronal loss and cognitive deficit. Treatment in the early stages of the disease is crucial for preventing or perhaps reversing the neurodegeneration in the AD cases. However, none of the current diagnostic procedures are capable of early diagnosis of AD. Further, the available treatments merely provide symptomatic alleviation in AD and do not address the underlying illness. Therefore, there is no permanent cure for AD currently. Better therapeutic outcomes need the optimum drug concentration in the central nervous system (CNS) by traversing blood-brain-barrier (BBB). Nanotechnology offers enormous promise to transform the treatment and diagnostics of neurodegenerative diseases. Nanotechnology based diagnostic tools, drug delivery systems and theragnostic are capable of highly sensitive molecular detection, effective drug targeting and their combination. Significant work has been done in this area over the last decade and prospective results have been obtained in AD therapy. This review explores the various applications of nanotechnology in addressing the varied facets of AD, ranging from early detection to therapeutic interventions. This review also looks at how nanotechnology can help with the development of disease-modifying medicines, such as the delivery of anti-amyloid, anti-tau, cholinesterase inhibitors, antioxidants and hormonal drugs. In conclusion, this paper discusses the role of nanotechnology in the early detection of AD, effective drug targeting to the CNS and theragnostic applications in the management of AD.
    Keywords:  Alzheimer's disease; Amyloid plaques; Nano-diagnostics; Nanomedicine; Nanoparticles; Nanotechnology; Nanotherapeutics; Quantum dots; Theragnostic
    DOI:  https://doi.org/10.1016/j.bbagen.2024.130559
  7. Nat Commun. 2024 Jan 09. 15(1): 358
    A full-body transcription factor expression atlas with completely resolved cell identities in C. elegans.
    Yongbin Li, Siyu Chen, Weihong Liu, Di Zhao, Yimeng Gao, Shipeng Hu, Hanyu Liu, Yuanyuan Li, Lei Qu, Xiao Liu.
      Invariant cell lineage in C. elegans enables spatiotemporal resolution of transcriptional regulatory mechanisms controlling the fate of each cell. Here, we develop RAPCAT (Robust-point-matching- And Piecewise-affine-based Cell Annotation Tool) to automate cell identity assignment in three-dimensional image stacks of L1 larvae and profile reporter expression of 620 transcription factors in every cell. Transcription factor profile-based clustering analysis defines 80 cell types distinct from conventional phenotypic cell types and identifies three general phenotypic modalities related to these classifications. First, transcription factors are broadly downregulated in quiescent stage Hermaphrodite Specific Neurons, suggesting stage- and cell type-specific variation in transcriptome size. Second, transcription factor expression is more closely associated with morphology than other phenotypic modalities in different pre- and post-differentiation developmental stages. Finally, embryonic cell lineages can be associated with specific transcription factor expression patterns and functions that persist throughout postembryonic life. This study presents a comprehensive transcription factor atlas for investigation of intra-cell type heterogeneity.
    DOI:  https://doi.org/10.1038/s41467-023-42677-6
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