Drug discovery: Insights from the invertebrate <i>Caenorhabditis elegans</i>

Giunti, Sebastián; Andersen, Natalia Denise; Rayes, Diego; Rosa, Maria Jose de

doi:10.1002/prp2.721

Cited by 66 publications

(49 citation statements)

References 226 publications

(379 reference statements)

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“…Not only are the genetic cascades of the core apoptotic machinery conserved between humans and worms, but many regulators of cell clearance have homologs in mammals [241]. As C. elegans is often used for large-scale drug screens in many biological aspects [257], conserved components of the phagocytic machinery potentially allow using the worm as a model to test drugs, which enhance or inhibit phagocytosis.…”

Section: Discussionmentioning

confidence: 99%

Conserved and Distinct Elements of Phagocytosis in Human and C. elegans

Lukácsi

Farkas

Saskői

et al. 2021

IJMS

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Endocytosis provides the cellular nutrition and homeostasis of organisms, but pathogens often take advantage of this entry point to infect host cells. This is counteracted by phagocytosis that plays a key role in the protection against invading microbes both during the initial engulfment of pathogens and in the clearance of infected cells. Phagocytic cells balance two vital functions: preventing the accumulation of cell corpses to avoid pathological inflammation and autoimmunity, whilst maintaining host defence. In this review, we compare elements of phagocytosis in mammals and the nematode Caenorhabditis elegans. Initial recognition of infection requires different mechanisms. In mammals, pattern recognition receptors bind pathogens directly, whereas activation of the innate immune response in the nematode rather relies on the detection of cellular damage. In contrast, molecules involved in efferocytosis—the engulfment and elimination of dying cells and cell debris—are highly conserved between the two species. Therefore, C. elegans is a powerful model to research mechanisms of the phagocytic machinery. Finally, we show that both mammalian and worm studies help to understand how the two phagocytic functions are interconnected: emerging data suggest the activation of innate immunity as a consequence of defective apoptotic cell clearance.

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Section: Discussionmentioning

confidence: 99%

Conserved and Distinct Elements of Phagocytosis in Human and C. elegans

Lukácsi

Farkas

Saskői

et al. 2021

IJMS

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“…Third, it has been challenging to devise novel therapeutic strategies for WS. Early phases of drug discovery and compound screening for this currently incurable disease may be achieved using this nematode platform [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

MUT-7 Provides Molecular Insight into the Werner Syndrome Exonuclease

Hsu

Chen

et al. 2021

Cells

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Werner syndrome (WS) is a rare recessive genetic disease characterized by premature aging. Individuals with this disorder develop normally during childhood, but their physiological conditions exacerbate the aging process in late adolescence. WS is caused by mutation of the human WS gene (WRN), which encodes two main domains, a 3′-5′ exonuclease and a 3′-5′ helicase. Caenorhabditis elegans expresses human WRN orthologs as two different proteins: MUT-7, which has a 3′-5′ exonuclease domain, and C. elegans WRN-1 (CeWRN-1), which has only helicase domains. These unique proteins dynamically regulate olfactory memory in C. elegans, providing insight into the molecular roles of WRN domains in humans. In this review, we specifically focus on characterizing the function of MUT-7 in small interfering RNA (siRNA) synthesis in the cytoplasm and the roles of siRNA in directing nuclear CeWRN-1 loading onto a heterochromatin complex to induce negative feedback regulation. Further studies on the different contributions of the 3′-5′ exonuclease and helicase domains in the molecular mechanism will provide clues to the accelerated aging processes in WS.

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“…About half of C. elegans' protein-coding genes have functional counterparts (orthologs) in humans. 4 Dr Saul notes that the exact proportion depends on the algorithm used to analyse the relationships. "Nevertheless, the risk of finding false negatives and false positives is quite high.…”

Section: Our Genetic Footprintmentioning

confidence: 99%

What has Caenorhabditis elegans ever done for us?

Greener¹

2021

Prescriber

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I n your compost heap or on the fruit rotting at the bottom of your garden lives a tiny worm called Caenorhabditis elegans. 1 Since the worm's discovery by the French zoologist Émile Maupas in 1897, studies of C. elegans have transformed biological science and led to three Nobel prizes (see Box 1). 1 "This small worm is one of the most popular model organisms in biological studies," says Dr Nadine Saul, a Biochemist at the Humboldt University of Berlin. "Biologists use C. elegans for, among others, pharmacological screenings, basic medical research, ecological studies and to uncover genetic principles."Studies of C. elegans, which is just 1-2mm long as an adult, led to several biological firsts. 1 In 1998, C. elegans became the first multicellular organism with a complete published genome sequence. 2 An adult hermaphrodite C. elegans expresses 302 neurones and 56 glial cells, which typically show the same cellcell connections between individual worms. 3 C. elegans remains the only organism in which researchers have established the complete neural wiring. 4 "C. elegans also enabled the understanding of several fundamental biological processes, including many of the genes and pathways important in apoptosis [controlled cell death]," says Professor María José De Rosa from the Universidad Nacional del Sur, Argentina and an independent researcher at INIBIBB-CONICET, Buenos Aires. "C. elegans are transparent. So, it was possible to express, for the first time, green fluorescent protein [GFP] in a living organism." GFP allows researchers to identify cells containing tagged recombinant DNA and to localise specific proteins.Apart from apoptosis, research using C. elegans helped unravel the genetic basis of pathways involved in, for example, development, ageing and RNA-mediated interference. 5 The worm was pivotal to the discovery of microRNAs, which regulate protein transcription in all organisms. 6 More recently, C. elegans has become increasingly important in large-scale drug screening and as a model for conditions as diverse as cancer,

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Drug discovery: Insights from the invertebrate Caenorhabditis elegans

Cited by 66 publications

References 226 publications

Conserved and Distinct Elements of Phagocytosis in Human and C. elegans

Conserved and Distinct Elements of Phagocytosis in Human and C. elegans

MUT-7 Provides Molecular Insight into the Werner Syndrome Exonuclease

What has Caenorhabditis elegans ever done for us?

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