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Glucose hypometabolism and glial activation are pathological features seen in AD brains; however, the connection between the two is not fully understood. Using a Drosophila model of AD, we identified that glucose metabolism in glia plays a critical role in neuroinflammation under disease conditions. Expression of human MATP (hereafter referred to as Tau) in the retinal cells, including photoreceptor neurons and pigment glia, causes photoreceptor degeneration accompanied by the formation of dark-stained round inclusion-like structures and swelling of the lamina cortex. We found that inclusion-like structures are formed by glial phagocytosis, and swelling of the laminal cortex correlates with the expression of antimicrobial peptides. Coexpression of human glucose transporter 3 (SLC2A3, hereafter referred to as GLUT3) with Tau in the retina does not affect Tau levels but suppresses these inflammatory responses and photoreceptor degeneration. We also found that expression of GLUT3, specifically in the pigment glia, is sufficient to suppress inflammatory phenotypes and mitigate photoreceptor degeneration in the Tau-expressing retina. Our results suggest that glial glucose metabolism contributes to inflammatory responses and neurodegeneration in tauopathy.<\/jats:p>","DOI":"10.1242\/dmm.052057","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T08:04:38Z","timestamp":1743149078000},"source":"Crossref","is-referenced-by-count":6,"title":["Glucose uptake in pigment glia suppresses Tau-induced inflammation and photoreceptor degeneration"],"prefix":"10.1242","volume":"18","author":[{"given":"Mikiko","family":"Oka","sequence":"first","affiliation":[{"name":"Tokyo Metropolitan University 1 Department of Biological Sciences , , Tokyo 192-0397, Japan"},{"name":"Baylor College of Medicine 2 Department of Molecular and Human Genetics , , Houston, TX 77030, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute for Texas Children's Hospital 3 , Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan University 1 Department of Biological Sciences , , Tokyo 192-0397, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan University 1 Department of Biological Sciences , , Tokyo 192-0397, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine 2 Department of Molecular and Human Genetics , , Houston, TX 77030, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute for Texas Children's Hospital 3 , Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3956-276X","authenticated-orcid":false,"given":"Kanae","family":"Ando","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan University 1 Department of Biological Sciences , , Tokyo 192-0397, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"2025042903444282300_DMM052057C1","doi-asserted-by":"publisher","first-page":"e1007440","DOI":"10.1371\/journal.pgen.1007440","article-title":"Antimicrobial peptides modulate long-term memory","volume":"14","author":"Barajas-Azpeleta","year":"2018","journal-title":"PLoS Genet."},{"key":"2025042903444282300_DMM052057C2","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.cmet.2011.08.016","article-title":"Brain energy metabolism: Focus on astrocyte-neuron metabolic cooperation","volume":"14","author":"B\u00e9langer","year":"2011","journal-title":"Cell Metab."},{"key":"2025042903444282300_DMM052057C3","doi-asserted-by":"publisher","first-page":"e0118765","DOI":"10.1371\/journal.pone.0118765","article-title":"Enhanced neuronal glucose transporter expression reveals metabolic choice in a HD Drosophila model","volume":"10","author":"Besson","year":"2015","journal-title":"PLoS ONE"},{"key":"2025042903444282300_DMM052057C4","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/nri3763","article-title":"Immunity in Drosophila melanogaster--from microbial recognition to whole-organism physiology","volume":"14","author":"Buchon","year":"2014","journal-title":"Nat. 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