{
  "abstract": "Soil-transmitted helminthiasis affects more than a billion people worldwide and is a global health concern. With no effective vaccination available, treatment relies on mass administration of anthelmintic drugs, like albendazole, ivermectin, and levamisole. Unfortunately, their regular of overuse has given rise to resistance. Levamisole, a cholinergic agonist, activates the nematode L-type acetylcholine receptors and causes muscle contraction and worm paralysis. In parasitic nematodes, such as female Brugia malayi , worms paralyze and recover through cholinergic tachyphylaxis. In this study, we dissect the molecular mechanisms behind cholinergic tachyphylaxis using the free-living model, C. elegans . Here, we differentiate between two independent recovery mechanisms: one that is mediated by L-AChR clustering mutants – lev-10 and another, mediated by an ER-resident protein, NRA-2. Cholinergic tachyphylaxis observed in nra-2 mutants can be distinguished from lev-10 mutants using motility assays, transcript analysis, and calcium imaging. nra-2 mutants are more sensitive to levamisole and recover differently than lev-10 mutants. We observe that nra-2 mutants do not show increased calcium influx during their levamisole-mediated recovery. Our study delineates two distinct modes by which worms can adapt and overcome effects of cholinergic anthelmintics.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "Shruti Gupta"
    },
    {
      "name": "Jacob Wragge"
    },
    {
      "name": "Sudhanva Kashyap"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2kcb09hnvd9jb.bib",
  "cited_by": 0,
  "doi": "10.21203/rs.3.rs-11130925/v1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13734247/",
  "id": "2kcb09hnvd9jb",
  "issns": [
    "2693-5015"
  ],
  "landing_url": "https://doi.org/10.21203/rs.3.rs-11130925/v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Nicotinic Acetylcholine Receptors Study"
    ]
  ],
  "openalex": "W7223854008",
  "pdf_url": "https://www.researchsquare.com/article/rs-11130925/latest.pdf",
  "pmcid": "PMC13734247",
  "pmid": "42990728",
  "published": "2026-10-27",
  "publisher": "American Journal Experts",
  "ris": "https://research.draconitic.com/paper/2kcb09hnvd9jb.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:52Z",
      "native_id": "PMC13734247",
      "source": "pmc",
      "url": "https://doi.org/10.21203/rs.3.rs-11130925/v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Nicotinic Acetylcholine Receptors Study",
      "subfield": "molecular-biology"
    }
  ],
  "title": "LEV-10 and NRA-2 regulate distinct mechanisms of cholinergic tachyphylaxis in Caenorhabditis elegans",
  "title_text": "LEV-10 and NRA-2 regulate distinct mechanisms of cholinergic tachyphylaxis in Caenorhabditis elegans",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:52Z",
  "url": "https://research.draconitic.com/paper/2kcb09hnvd9jb",
  "venue": "Research Square",
  "versions": []
}