{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:51:09Z","timestamp":1791571869718,"version":"4.3.4"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"41","funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["543\/21"],"award-info":[{"award-number":["543\/21"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["2505\/24"],"award-info":[{"award-number":["2505\/24"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["942\/25"],"award-info":[{"award-number":["942\/25"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology, Israel","doi-asserted-by":"publisher","award":["80884"],"award-info":[{"award-number":["80884"]}],"id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Henri J. and Erna D. Leir Chair","award":["Research in Neurodegenerative Diseases"],"award-info":[{"award-number":["Research in Neurodegenerative Diseases"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:p>\n                    The proteostasis network (PN) safeguards the integrity of proteins by promoting various cellular activities. However, with aging, the PN\u2019s competence declines and aggregated proteins accrue within cells. This process underlies the development of neurodegenerative disorders such as Alzheimer\u2019s and Huntington\u2019s 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\n                    <jats:italic toggle=\"yes\">gtr-1<\/jats:italic>\n                    , which encodes a neuronal heterotrimeric guanine nucleotide\u2013binding protein\u2013coupled receptor, mitigates the toxicity of the Alzheimer\u2019s disease cause, A\u03b2 peptide. Here, we investigated the mechanism that is acted upon the knockdown of\n                    <jats:italic toggle=\"yes\">gtr-1<\/jats:italic>\n                    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\n                    <jats:italic toggle=\"yes\">gtr-1<\/jats:italic>\n                    also enhances protein degradation. These findings highlight the roles of neuropeptides as organismal coordinators of proteostasis in the face of distinct proteotoxic challenges.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ady6048","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:06:59Z","timestamp":1791569219000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["A neuronal GPCR modifies neuropeptide signaling to suppress proteostasis in distal tissues"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9023-8158","authenticated-orcid":true,"given":"Joud","family":"Hirbawi","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel\u2013Canada, The Hebrew University of Jerusalem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0323-0413","authenticated-orcid":true,"given":"Adam","family":"Zaretsky","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel\u2013Canada, The Hebrew University of Jerusalem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huadong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel\u2013Canada, The Hebrew University of Jerusalem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri","family":"Goshtchevsky","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel\u2013Canada, The Hebrew University of Jerusalem, Jerusalem, 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Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irit","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel\u2013Canada, The Hebrew University of Jerusalem, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9374-2489","authenticated-orcid":true,"given":"Galia","family":"Blum","sequence":"additional","affiliation":[{"name":"Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5552-7086","authenticated-orcid":true,"given":"Ehud","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel\u2013Canada, The Hebrew University of Jerusalem, Jerusalem, 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