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Cell,
1996]
The process of aging influences our poetry, our art, our lifestyle, and our happiness, yet we know surprisingly little about it. Genetics has taught us a great deal about gene regulation, development, and the cell cycle. Can it teach us how we age?
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Trends Parasitol,
2009]
Neuropeptides are small messenger molecules that can be found in all metazoans, where they govern a diverse array of physiological processes. Because neuropeptides seem to be conserved among pest species, selected peptides can be considered as attractive targets for drug discovery. Much can be learned from the model system Caenorhabditis elegans because of the availability of a sequenced genome and state-of-the-art postgenomic technologies that enable characterization of endogenous peptides derived from neuropeptide-like protein (NLP) precursors. Here, we provide an overview of the NLP peptide family in C. elegans and discuss their resemblance with arthropod neuropeptides and their relevance for anthelmintic discovery.
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WormBook,
2006]
The simple and well-defined structure of the C. elegans nervous system has made it an attractive model for studying the neural and genetic basis of behavior. However, the wider use physiological methods for monitoring neural activity in vivo or determining the effects of specific ion channels on neuronal function has been a relatively recent development. This chapter presents a compendium of protocols and technical reports on the current state of the art in C. elegans electrophysiology and neuroimaging. These include methods for calcium imaging in intact animals, in situ electrical recording from neurons and muscle cells, and in vitro recording from cultured neurons and oocytes.
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Cell Mol Life Sci,
2012]
In addition to its central roles in protein quality control, regulation of cell cycle, intracellular signaling, DNA damage response and transcription regulation, the ubiquitin-proteasome system (UPS) plays specific roles in the nervous system, where it contributes to precise connectivity through development, and later assures functionality by regulating a wide spectrum of neuron-specific cellular processes. Aberrations in this system have been implicated in the etiology of neurodevelopmental and neurodegenerative diseases. In this review, we provide an updated view on the UPS and highlight recent findings concerning its role in normal and diseased nervous systems. We discuss the advantages of the model organism Caenorhabditis elegans as a tool to unravel the major unsolved questions concerning this biochemical pathway and its involvement in nervous system function and dysfunction, and expose the new possibilities, using state-of-the-art techniques, to assess UPS function using this model system.
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Neurosci Res,
2017]
Many mammalian species, including humans, spend a substantial fraction of their life sleeping. Sleep deprivation in rats ultimately leads to death, indicating the essential role of sleep. Exactly why sleep is so essential, however, remains largely unknown. From an evolutionary point of view, almost all animal species that have been investigated exhibit sleep or sleep-like states, suggesting that sleep may benefit survival. In certain mammalian and avian species, sleep can be further divided into at least two stages, rapid eye movement (REM) sleep and non-REM sleep. In addition to a widely conserved role for sleep, these individual sleep stages may have roles unique to these animals. The recent use of state-of-the-art techniques, including optogenetics and chemogenetics, has greatly broadened our understanding of the neural mechanisms of sleep regulation, allowing us to address the function of sleep. Studies focusing on non-mammalian animals species have also provided novel insights into the evolution of sleep. This review provides a comprehensive overview regarding the current knowledge of the function and evolution of sleep.
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Front Endocrinol (Lausanne),
2012]
The G-protein coupled receptor (GPCR) family is comprised of seven transmembrane domain proteins and play important roles in nerve transmission, locomotion, proliferation and development, sensory perception, metabolism, and neuromodulation. GPCR research has been targeted by drug developers as a consequence of the wide variety of critical physiological functions regulated by this protein family. Neuropeptide GPCRs are the least characterized of the GPCR family as genetic systems to characterize their functions have lagged behind GPCR gene discovery. Drosophila melanogaster and Caenorhabditis elegans are genetic model organisms that have proved useful in characterizing neuropeptide GPCRs. The strength of a genetic approach leads to an appreciation of the behavioral plasticity that can result from subtle alterations in GPCRs or regulatory proteins in the pathways that GPCRs control. Many of these invertebrate neuropeptides, GPCRs, and signaling pathway components serve as models for mammalian counterparts as they have conserved sequences and function. This review provides an overview of the methods to match neuropeptides to their cognate receptor and a state of the art account of neuropeptide GPCRs that have been characterized in D. melanogaster and C. elegans and the behaviors that have been uncovered through genetic manipulation.
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Redox Biol,
2024]
Oxidative stress is a crucial concept in redox biology, and significant progress has been made in recent years. Excessive levels of reactive oxygen species (ROS) can lead to oxidative damage, heightening vulnerability to various diseases. By contrast, ROS maintained within a moderate range plays a role in regulating normal physiological metabolism. Choosing suitable animal models in a complex research context is critical for enhancing research efficacy. While rodents are frequently utilized in medical experiments, they pose challenges such as high costs and ethical considerations. Alternatively, non-rodent model organisms like zebrafish, Drosophila, and C. elegans offer promising avenues into oxidative stress research. These organisms boast advantages such as their small size, high reproduction rate, availability for live imaging, and ease of gene manipulation. This review highlights advancements in the detection of oxidative stress using non-rodent models. The oxidative homeostasis regulatory pathway, Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2), is systematically reviewed alongside multiple regulation of Nrf2-centered pathways in different organisms. Ultimately, this review conducts a comprehensive comparative analysis of different model organisms and further explores the combination of novel techniques with non-rodents. This review aims to summarize state-of-the-art findings in oxidative stress research using non-rodents and to delineate future directions.
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Acta Trop,
2020]
This review summarises more than a century of research on onchocerciasis, also known as river blindness, and its control. River blindness is an infection caused by the tissue filaria Onchocerca volvulus affecting the skin, subcutaneous tissue and eyes and leading to blindness in a minority of infected persons. The parasite is transmitted by its intermediate hosts Simulium spp. which breed in rivers. Featured are history and milestones in onchocerciasis research and control, state-of-the-art data on the parasite, its endobacteria Wolbachia, on the vectors, previous and current prevalence of the infection, its diagnostics, the interaction between the parasite and its host, immune responses and the pathology of onchocerciasis. Detailed information is documented on the time course of control programmes in the afflicted countries in Africa and the Americas, a long road from previous programmes to current successes in control of the transmission of this infectious disease. By development, adjustment and optimization of the control measures, transmission by the vector has been interrupted in foci of countries in the Americas, in Uganda, in Sudan and elsewhere, followed by onchocerciasis eliminations. The current state and future perspectives for control, elimination and eradication within the next 20-30 years are described and discussed. This review contributes to a deeper comprehension of this disease by a tissue-dwelling filaria and it will be helpful in efforts to control and eliminate other filarial infections.
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Prog Neurobiol,
2007]
The nematode Caenorhabditis elegans joins the menagerie of behavioral model systems next to the fruit fly Drosophila melanogaster, the marine snail Aplysia californica and the mouse. In contrast to Aplysia, which contains 20,000 neurons having cell bodies of hundreds of microns in diameter, C. elegans harbors only 302 tiny neurons from which the cell lineage is completely described, as is the case for all the other somatic cells. As such, this nervous system appears at first sight incommensurable with those of higher organisms, although genome-wide comparison of predicted C. elegans genes with their counterparts in vertebrates revealed many parallels. Together with its short lifespan and ease of cultivation, suitability for high-throughput genetic screenings and genome-wide RNA interference approaches, access to an advanced genetic toolkit and cell-ablation techniques, it seems that this tiny transparent organism of only 1mm in length has nothing to hide. Recently, highly exciting developments have occurred within the field of neuropeptidergic signaling in C. elegans, not only because of the availability of a sequenced genome since 1998, but especially because of state of the art post genomic technologies, that allow for molecular characterization of the signaling molecules. Here, we will focus on endogenous, bioactive (neuro)peptides and mainly discuss biosynthesis, peptide sequence information, localization and G-protein coupled receptors of the three major peptide families in C. elegans.
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Biochim Biophys Acta,
2016]
Testing the predictions of the Mitochondrial Free Radical Theory of Ageing (MFRTA) has provided a deep understanding of the role of reactive oxygen species (ROS) and mitochondria in the aging process. However those data, which support MFRTA are in the majority correlative (e.g. increasing oxidative damage with age). In contrast the majority of direct experimental data contradict MFRTA (e.g. changes in ROS levels do not alter longevity as expected). Unfortunately, in the past, ROS measurements have mainly been performed using isolated mitochondria, a method which is prone to experimental artifacts and does not reflect the complexity of the in vivo process. New technology to study different ROS (e.g. superoxide or hydrogen peroxide) in vivo is now available; these new methods combined with state-of-the-art genetic engineering technology will allow a deeper interrogation of, where, when and how free radicals affect aging and pathological processes. In fact data that combine these new approaches, indicate that boosting mitochondrial ROS in lower animals is a way to extend both healthy and maximum lifespan. In this review, I discuss the latest literature focused on the role of mitochondrial ROS in aging, and how these new discoveries are helping to better understand the role of mitochondria in health and disease. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.