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The combination of 5-aminolevulinic acid (5-ALA) and sodium ferrous citrate (SFC) is known to improve mitochondrial functions. Here, we report that 5-ALA combined with SFC (5-ALA\/SFC) improves mitochondrial functions and mitigates neurodegeneration in transgenic Drosophila expressing human tau. We found that tau reduces ATP levels, decreases mitochondrial distribution to neurites, and increases mitochondrial reactive oxygen species (ROS). Expression of oxidative phosphorylation (OXPHOS) genes was upregulated, and activities of complexes I and IV were elevated. Feeding 5-ALA\/SFC to tau flies lowers oxidative damage without correcting OXPHOS activities or mitochondrial distribution. 5-ALA\/SFC treatment suppressed pathological tau phosphorylation and mitigated tau-induced neurodegeneration. These results suggest that 5-ALA\/SFC attenuates a neurodegenerative pathway involving tau, mitochondria, and ROS.<\/jats:p>","DOI":"10.3390\/life16050725","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:34:42Z","timestamp":1777458882000},"page":"725","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["5-ALA\/SFC Mitigates Tau Toxicity via Lowering Oxidative Stress in a Drosophila Model of Tau Toxicity"],"prefix":"10.3390","volume":"16","author":[{"given":"Arisa","family":"Tamura","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Nozawa","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Research, SBI Pharmaceuticals Co., Ltd., Tokyo 106-6020, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4005-0542","authenticated-orcid":false,"given":"Emiko","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3956-276X","authenticated-orcid":false,"given":"Kanae","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan"},{"name":"Department of Biological Sciences, Faculty of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2025). 2025 Alzheimer\u2019s disease facts and figures. 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