Toxicity arising from protein misfolding and aggregation (proteotoxicity) is tightly mechanistically linked to the emergence of late-onset neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Why these maladies manifest in late stages of life and what mechanisms protect the young organism from disease are key enigmas. The nematode Caenorhabditis elegans offers key advantages that enable systematic exploration of many cell biological and functional aspects of neurodegeneration-linked proteotoxicity. Here we review the abundantly used nematode-based proteotoxicity models and delineate common techniques for the measurement of protein aggregation and rate of proteotoxicity. We also discuss the advantages offered by the worm for genetic screening, drug development and for the exploration of the links between proteotoxicity and the aging process.
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http://dx.doi.org/10.1016/j.ymeth.2014.04.014 | DOI Listing |
Mar Pollut Bull
January 2025
Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei 106, Taiwan. Electronic address:
Emerging contaminants in estuarine sediments, such as bis(2-ethylhexyl) phthalate (DEHP) and titanium dioxide nanoparticles (nTiO), pose ecotoxicological risks that may be exacerbated by co-contamination. This study investigated the impacts of DEHP, nTiO, and their combinations at environmentally relevant concentrations (1, 10, and 100 μg/g) on the soil nematode Caenorhabditis elegans in estuarine-like sediment (14.25‰ salinity).
View Article and Find Full Text PDFChem Biol Interact
January 2025
Key Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China. Electronic address:
Copper, as a vital trace element and ubiquitous environmental pollutant, exhibits a positive correlation with the neurodegenerative diseases. Recent studies have highlighted ferroptosis's significance in heavy metal-induced neurodegenerative diseases, yet its role in copper-related neurotoxicity remains unclear. This study aimed to investigate the role of ferroptosis in copper-induced neurotoxicity.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Karolinska Institutet, Solna, Sweden.
Background: High age is the biggest risk factor for Alzheimer's disease (AD). Approved drugs that slow down the aging process have the potential to be repurposed for the primary prevention of AD. The aim of our project was to use a reverse translational approach to identify such drug candidates in epidemiological data followed by validation in cell-based models and animal models of aging and AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Background: The molecular mechanisms associated with Alzheimer's Disease (AD) have been extensively studied in mouse models (Mus musculus). However, experimental research in these models is costly and time-consuming. In this context, the nematode Caenorhabditis elegans (C.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Washington, Seattle, WA, USA.
Background: Genetic variation of lysosomal protein, transmembrane protein 106B (TMEM106B) has long been known as a risk factor for a diverse range of neurodegenerative disorders, especially FTLD with progranulin (GRN) haplo-insufficiency, though the mechanisms involved are not yet understood. Recently, through advances in cryo-electron microscopy (cryo-EM), aggregates of the C-Terminal domain of TMEM106B (TMEM CT) were shown to make up previously unidentifiable protein aggregates in the brains of human FTLD, AD, progressive supranuclear palsy (PSP), and dementia with Lewy Bodies (DLB) patients.
Methods: To determine the TMEM CT aggregation propensity and neurodegenerative potential, we generated a new transgenic C.
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