Subject collection: C. elegans
- Interpreting the pathogenicity of Joubert syndrome missense variants in Caenorhabditis elegans
Editor’s choice: Genome editing was carried out in C. elegans to model and characterise two pathogenic missense variants of mksr-2/B9D2, P74S and G155S, from a compound heterozygous patient with Joubert syndrome.
- Modulating the endoplasmic reticulum stress response attenuates neurodegeneration in a Caenorhabditis elegans model of spinal muscular atrophy
Summary: A new non-larval-lethal C. elegans model of spinal muscular atrophy shows mild phenotypes, such as muscle cell and neuronal degeneration, and is therefore useful for testing potential drug treatments.
- Modeling neurodegeneration in Caenorhabditis elegans
Summary: While unsurpassed as an experimental system for fundamental biology, Caenorhabditis elegans remains undervalued for its translational potential. Here, we highlight significant outcomes from, and resources available for, C. elegans-based research into neurodegenerative disorders.
- The SDHB Arg230His mutation causing familial paraganglioma alters glycolysis in a new Caenorhabditis elegans model
Editor’s choice: Heritable pheochromocytoma/paraganglioma follows the Arg230His missense mutation in SDHB in mitochondrial complex II. By mutating this highly conserved ortholog in C. elegans, we generated a tractable phenotype.
- Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG
Editor's choice: Drug repurposing screens using worm and patient fibroblast models of PMM2-CDG led to the discovery of epalrestat, the first activator of PMM2 that targets the root cause of disease.
- Drug screens of NGLY1 deficiency in worm and fly models reveal catecholamine, NRF2 and anti-inflammatory-pathway activation as potential clinical approaches
Summary: Using worm and fly models of an ultra-rare congenital disorder of glycosylation, we performed repurposing screens and identified the FDA-approved drug aripiprazole as a clinical candidate.
- ApoE-associated modulation of neuroprotection from Aβ-mediated neurodegeneration in transgenic Caenorhabditis elegans
Summary: We report new humanized nematode models of amyloid-beta and apolipoprotein E gene expression, examining readouts for neurodegeneration, behavior, cellular function and survival, to elucidate the relative contributions of the proteins to the underlying pathology of Alzheimer's disease.
- Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of Caenorhabditis elegans and its functional response to drugs
Editor's choice: Dystrophin-deficient Caenorhabditis elegans have measurably weak muscle strength and mitochondrial dysfunction, and they respond to drug treatments standard in treating human Duchenne muscular dystrophy.
- CRISPR-Cas9 human gene replacement and phenomic characterization in Caenorhabditis elegans to understand the functional conservation of human genes and decipher variants of uncertain significance
Summary: Here, we provide a CRISPR-Cas9 human gene replacement and phenomic characterization strategy to directly replace Caenorhabditis elegans genes with their human orthologs for disease variant modeling and therapeutic screening.