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Exp Gerontol,
2006]
Caenorhabditis elegans has been used to model aspects of a number of age-associated neurodegenerative diseases, including Alzheimer''s, Parkinson''s and Huntington''s diseases. These models have typically involved the transgenic expression of disease-associated human proteins. Here I describe my laboratory''s specific experience engineering C. elegans models of Alzheimer''s disease, and give a general consideration of the advantages and disadvantages of these C. elegans models. The type of insights that might be gained from using these (relatively) simple models are highlighted. In particular, I consider the potential these models have for uncovering common and unique fundamental toxic mechanisms underlying human neurodegenerative diseases.
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Curr Biol,
2001]
When meiotic cells complete S phase, homologous chromosomes pair, synapse and undergo recombination. A checkpoint protein is somehow required for meiotic chromosome pairing in C. elegans, thus providing a direct link between S phase and the rest of the meiotic program.
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Toxins (Basel),
2016]
Staphylococcus aureus is an opportunistic pathogen and the leading cause of a wide range of severe clinical infections. The range of diseases reflects the diversity of virulence factors produced by this pathogen. To establish an infection in the host, S. aureus expresses an inclusive set of virulence factors such as toxins, enzymes, adhesins, and other surface proteins that allow the pathogen to survive under extreme conditions and are essential for the bacteria's ability to spread through tissues. Expression and secretion of this array of toxins and enzymes are tightly controlled by a number of regulatory systems. S. aureus is also notorious for its ability to resist the arsenal of currently available antibiotics and dissemination of various multidrug-resistant S. aureus clones limits therapeutic options for a S. aureus infection. Recently, the development of anti-virulence therapeutics that neutralize S. aureus toxins or block the pathways that regulate toxin production has shown potential in thwarting the bacteria's acquisition of antibiotic resistance. In this review, we provide insights into the regulation of S. aureus toxin production and potential anti-virulence strategies that target S. aureus toxins.
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Future Med Chem,
2010]
Filariasis is caused by thread-like nematode worms, classified according to their presence in the vertebrate host. The cutaneous group includes Onchocerca volvulus, Loa loa and Mansonella streptocerca; the lymphatic group includes Wuchereria bancrofti, Brugia malayi and Brugia timori and the body cavity group includes Mansonella perstans and Mansonella ozzardi. Lymphatic filariasis, a mosquito-borne disease, is one of the most prevalent diseases in tropical and subtropical countries and is accompanied by a number of pathological conditions. In recent years, there has been rapid progress in filariasis research, which has provided new insights into the pathogenesis of filarial disease, diagnosis, chemotherapy, the host-parasite relationship and the genomics of the parasite. Together, these insights are assisting the identification of novel drug targets and the discovery of antifilarial agents and candidate vaccine molecules. This review discusses the antifilarial activity of various chemical entities, the merits and demerits of antifilarial drugs currently in use, their mechanisms of action, in addition to antifilarial drug targets and their validation.
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WormBook,
2007]
Because of their free-living life cycle alternatives, Strongyloides and related nematode parasites may represent the best models for translating C. elegans science to the study of nematode parasitism. S. stercoralis, a significant pathogen of humans, can be maintained in laboratory dogs and gerbils. Biosafety precautions necessary for work with S. stercoralis, though unfamiliar to many C. elegans researchers, are straightforward and easily accomplished. Although specialized methods are necessary for large-scale culture of the free-living stages of S. stercoralis, small-scale cultures for experimental purposes may be undertaken using minor modifications of standard C. elegans methods. Similarly, the morphological similarities between C. elegans and the free-living stages of S. stercoralis allow investigational methods such as laser cell ablation and DNA transformation by gonadal microinjection to be easily adapted from C. elegans to S. stercoralis. Comparative studies employing these methods have yielded new insights into the neuronal control of the infective process in parasites and its similarity to regulation of dauer development in C. elegans. Furthermore, we have developed a practical method for transient transformation of S. stercoralis with vector constructs having various tissue- and cell-specific expression patterns and have assembled these into a modular vector kit for distribution to the community.
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Ann Pharm Fr,
2006]
The Nematode Caenorhabditis elegans (C. elegans) is an established model increasingly used for studying human disease pathogenesis. C. elegans models are based on the mutagenesis of human disease genes conserved in this Nematode or on the transgenesis with disease genes not conserved in C. elegans. Genetic examinations will give new insights on the cellular and molecular mechanisms that are altered in some neurodegenerative diseases like Duchenne''s muscular dystrophy, Huntington''s disease and Alzheimer''s disease. C. elegans may be used for primary screening of new compounds that may be used as drugs in these diseases.
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Mol Cell,
2004]
Applying a combination of innovative approaches to understanding neuronal gene regulation in C. elegans, an article in the latest Developmental Cell (Wenick and Hobert, 2004) gives hope that reading the genome''s transcriptional regulatory code may one day be possible.
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Front Biosci,
2004]
Alzheimer''s disease (AD) is affecting more people every year due to the increase in elderly population. This disease is characterized by senior plaques, containing aggregated amyloid beta peptide (A beta), and neurofibrillary tangles in the AD brains. The A beta depositions are thought to increase in cellular oxidative stress, which subsequently produces neuronal cell death in the patient s brain, causing loss of memory and, in the latter stages, dementia. Diverse models have been established to test this, "Amyloid Toxicity Hypothesis of AD". Among these, the use of the nematode Caenorhabditis elegans has some advantages. This invertebrate has its entire genome known, as well as numerous gene homologues to those seen in humans. In relationship with the cell model, the nematode gives the benefit of an organismal view of the disease. The nematode''s short life span proves useful, when compared with that of mice, allowing mechanistic studies of the disease and pharmacological treatments. Alongside with other laboratories, we have used this in vivo model to correlate the Abeta expression with its toxicity through the observance of the organism''s behavior to provide a better understanding of the cellular processes underlining AD.
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Neurodegener Dis,
2007]
Parkinson''s disease (PD) is one of the most common age-related neurodegenerative diseases that is characterized by selective loss of dopaminergic neurons. Despite recent findings from mammalian model systems, molecular mechanisms of the pathophysiology are poorly understood. Given the high conservation of molecular pathways from invertebrates to mammalians, combined with technical advantages, such as high-throughput approaches, Caenorhabditis elegans represents a powerful system for the identification of factors involved in neurodegeneration. In this review we describe that C. elegans can be used to advance our understanding of the genetic mechanisms implicated in these disorders. Copyright (c) 2007 S. Karger AG, Basel.
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Curr Biol,
2005]
Aurora B kinases play important roles during mitosis in eukaryotic cells; new work in Caenorhabditis elegans has identified the Tousled kinase TLK-1 as a substrate activator of the model nematode''''s Aurora B kinase AIR-2 which acts to ensure proper chromosome segregation during