{
  "abstract": "The proteostasis network (PN) safeguards the integrity of proteins by promoting various cellular activities. However, with aging, the PN’s competence declines and aggregated proteins accrue within cells. This process underlies the development of neurodegenerative disorders such as Alzheimer’s and Huntington’s diseases. While the PN functions within cells, proteostasis is regulated across the organism by intertissue communication, which is partially governed by neurons. We previously found that reducing the expression of gtr-1 , which encodes a neuronal heterotrimeric guanine nucleotide–binding protein–coupled receptor, mitigates the toxicity of the Alzheimer’s disease cause, Aβ peptide. Here, we investigated the mechanism that is acted upon the knockdown of gtr-1 and found that it differentially modulates gene expression profiles, including of neuropeptide-coding genes, and dissimilarly modifies protein aggregation in worms that express distinct proteotoxic proteins. The knockdown of gtr-1 also enhances protein degradation. These findings highlight the roles of neuropeptides as organismal coordinators of proteostasis in the face of distinct proteotoxic challenges.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel–Canada, The Hebrew University of Jerusalem, Jerusalem, Israel.",
    "Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem, Israel."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Joud Hirbawi",
      "orcid": "0009-0004-9023-8158"
    },
    {
      "affs": [
        0
      ],
      "name": "Adam Zaretsky",
      "orcid": "0009-0001-0323-0413"
    },
    {
      "affs": [
        0
      ],
      "name": "Huadong Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Uri Goshtchevsky"
    },
    {
      "affs": [
        1
      ],
      "name": "Gourab Dey",
      "orcid": "0000-0002-9570-5032"
    },
    {
      "affs": [
        1
      ],
      "name": "Emmanuelle Merquiol",
      "orcid": "0000-0001-5754-498X"
    },
    {
      "affs": [
        0
      ],
      "name": "Atif Ahmed Siddiqui"
    },
    {
      "affs": [
        0
      ],
      "name": "Irit Cohen"
    },
    {
      "affs": [
        1
      ],
      "name": "Galia Blum",
      "orcid": "0000-0002-9374-2489"
    },
    {
      "affs": [
        0
      ],
      "name": "Ehud Cohen",
      "orcid": "0000-0001-5552-7086"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/93dwh1ma46fb6.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.ady6048",
  "fulltext_url": null,
  "id": "93dwh1ma46fb6",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.ady6048",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1302|Genetics, Aging, and Longevity in Model Organisms"
    ]
  ],
  "openalex": "W7221152021",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/93dwh1ma46fb6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.ady6048",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.ady6048"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1302|Genetics, Aging, and Longevity in Model Organisms",
      "subfield": "cell-biology"
    }
  ],
  "title": "A neuronal GPCR modifies neuropeptide signaling to suppress proteostasis in distal tissues",
  "title_text": "A neuronal GPCR modifies neuropeptide signaling to suppress proteostasis in distal tissues",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/93dwh1ma46fb6",
  "venue": "Science Advances",
  "versions": []
}