Wen Q et al. (2018) Philos Trans R Soc Lond B Biol Sci "Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for body undulation."

Zhen M, Wen Q, Gao S

[Philos Trans R Soc Lond B Biol Sci, 2018]

The intrinsic oscillatory activity of central pattern generators underlies motor rhythm. We review and discuss recent findings that address the origin of <i>Caenorhabditis elegans</i> motor rhythm. These studies propose that the A- and mid-body B-class excitatory motor neurons at the ventral cord function as non-bursting intrinsic oscillators to underlie body undulation during reversal and forward movements, respectively. Proprioception entrains their intrinsic activities, allows phase-coupling between members of the same class motor neurons, and thereby facilitates directional propagation of undulations. Distinct pools of premotor interneurons project along the ventral nerve cord to innervate all members of the A- and B-class motor neurons, modulating their oscillations, as well as promoting their bi-directional coupling. The two motor sub-circuits, which consist of oscillators and descending inputs with distinct properties, form the structural base of dynamic rhythmicity and flexible partition of the forward and backward motor states. These results contribute to a continuous effort to establish a mechanistic and dynamic model of the <i>C. elegans</i> sensorimotor system. <i>C. elegans</i> exhibits rich sensorimotor functions despite a small neuron number. These findings implicate a circuit-level functional compression. By integrating the role of rhythm generation and proprioception into motor neurons, and the role of descending regulation of oscillators into premotor interneurons, this numerically simple nervous system can achieve a circuit infrastructure analogous to that of anatomically complex systems. <i>C. elegans</i> has manifested itself as a compact model to search for general principles of sensorimotor behaviours.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling <i>C. elegans</i> at cellular resolution'.

Link CD (2006) Exp Gerontol "C. elegans models of age-associated neurodegenerative diseases: lessons from transgenic worm models of Alzheimer's disease."

Link CD

[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.

Meier B et al. (2001) Curr Biol "Checkpoints: chromosome pairing takes an unexpected twist."

Ahmed S, Meier B

[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.

Chen L et al. (2024) Cells "Amyotrophic Lateral Sclerosis Mechanism: Insights from the Caenorhabditis elegans Models."

Gao S, Zhang S, Liu S, Chen L

[Cells, 2024]

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, <i>Caenorhabditis elegans</i> (<i>C. elegans</i>), has emerged as a potent tool for investigating the molecular and cellular dimensions of ALS pathogenesis. This review summarizes the contributions of <i>C. elegans</i> 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 <i>C. elegans</i> system in the realm of ALS research and point towards future investigations that could bridge the chasm between <i>C. elegans</i> foundational discoveries and clinical applications.

Kong C et al. (2016) Toxins (Basel) "Targeting Staphylococcus aureus Toxins: A Potential form of Anti-Virulence Therapy."

Nathan S, Neoh HM, Kong C

[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.

Lok JB (2007) WormBook "Strongyloides stercoralis: a model for translational research on parasitic nematode biology."

Lok JB

[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.

Savel J et al. (2006) Ann Pharm Fr "[A Nematode Nobel Prize: Caenorhabditis elegans]"

Savel J, Clostre F

[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.

Portman DS et al. (2004) Mol Cell "Toward the computable transcriptome."

Bohmann D, Portman DS

[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.

Gutierrez-Zepeda A et al. (2004) Front Biosci "Testing the amyloid toxicity hypothesis of Alzheimer's disease in transgenic Caenorhabditis elegans model."

Gutierrez-Zepeda A, Luo Y

[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.

Schmidt E et al. (2007) Neurodegener Dis "Caenorhabditis elegans as a model system for Parkinson's disease."

Baumeister R, Schmidt E, Seifert M

[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.