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Saccharides can exert these functions via dedicated intracellular transporters and through binding to cellular sensors, such as saccharide-binding receptors. Glucose homeostasis and saccharide signaling are emerging as important regulators of neurodegeneration. Here, we utilized a Drosophila model of Huntington\u2019s disease to examine the role of Glut1 (homologous to multiple human glucose transporters) and saccharide-binding receptors. We find that Glut1 knockdown increases the amount of huntingtin-polyQ protein aggregates during aging, whereas Glut1 upregulation has converse effects. RNAi screening identifies several saccharide-binding receptors that either increase or decrease the levels of huntingtin-polyQ protein aggregates. In particular, pathogenic polyglutamine aggregates are reduced by knockdown of the lectin domain-containing G-protein coupled receptor Cirl (Calcium-independent receptor for \u03b1-latrotoxin), orthologous to human ADGRL1 and ADGRL2. These findings indicate that glucose transporters and saccharide-binding receptors regulate proteostasis and neurodegeneration during aging.<\/jats:p>","DOI":"10.1093\/gerona\/glag153","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:47:16Z","timestamp":1780573636000},"source":"Crossref","is-referenced-by-count":0,"title":["Regulation of huntingtin-polyQ aggregation by glucose transporters and saccharide-binding receptors during aging in Drosophila"],"prefix":"10.1093","volume":"81","author":[{"given":"Mamta","family":"Rai","sequence":"first","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital , Memphis, Tennessee,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zane","family":"Coleman","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital , Memphis, Tennessee,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Curley","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital , Memphis, Tennessee,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-9555","authenticated-orcid":false,"given":"Fabio","family":"Demontis","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology, St. Jude Children\u2019s Research Hospital , Memphis, Tennessee,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"2026070316480412300_glag153-B1","doi-asserted-by":"publisher","first-page":"812222","DOI":"10.3389\/fnins.2022.812222","article-title":"Frontotemporal dementia and glucose metabolism","volume":"16","author":"Garrett","year":"2022","journal-title":"Front Neurosci"},{"key":"2026070316480412300_glag153-B2","doi-asserted-by":"publisher","first-page":"15005","DOI":"10.1038\/nrdp.2015.5","article-title":"Huntington disease","volume":"1","author":"Bates","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"2026070316480412300_glag153-B3","doi-asserted-by":"publisher","first-page":"101358","DOI":"10.1016\/j.arr.2021.101358","article-title":"Systemic manifestation and contribution of peripheral tissues to Huntington\u2019s disease pathogenesis","volume":"69","author":"Chuang","year":"2021","journal-title":"Ageing Res Rev"},{"key":"2026070316480412300_glag153-B4","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/0022-510x(89)90120-2","article-title":"Endocrine functions in Huntington\u2019s disease. 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