{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:36:03Z","timestamp":1792802163701,"version":"4.5.0"},"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2020R1I1A2074979"],"award-info":[{"award-number":["2020R1I1A2074979"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["NRF-2022R1A4A1018963"],"award-info":[{"award-number":["NRF-2022R1A4A1018963"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Konkuk University Researcher Fund","award":["2023-A019-0248"],"award-info":[{"award-number":["2023-A019-0248"]}],"id":[{"id":"https:\/\/ror.org\/025h1m602","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Fatty acid-binding proteins (FABPs) are small cytoplasmic proteins involved in intracellular lipid transport and bind free fatty acids, cholesterol, and retinoids. FABP3, the major neuronal FABP in the adult brain, is upregulated in the CSF of patients with Alzheimer\u2019s disease (AD). However, the precise role of neuronal FABPs in AD pathogenesis remains unclear. This study investigates the contribution of fabp, the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    homolog of FABP3 and FABP7, to amyloid \u03b2 (A\u03b2) pathology using a\n                    <jats:italic>Drosophila<\/jats:italic>\n                    model. Neuronal knockdown of\n                    <jats:italic>fabp<\/jats:italic>\n                    shortened the lifespan of flies and increased age-related protein aggregates in the brain. In an AD model,\n                    <jats:italic>fabp<\/jats:italic>\n                    knockdown in neurons increased A\u03b2 accumulation and A\u03b2-induced neurodegeneration, whereas\n                    <jats:italic>fabp<\/jats:italic>\n                    overexpression ameliorated A\u03b2 pathology. Notably,\n                    <jats:italic>fabp<\/jats:italic>\n                    overexpression stimulated autophagy, which was inhibited by the knockdown of\n                    <jats:italic>Eip75B<\/jats:italic>\n                    , the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    homolog of the peroxisome proliferator-activated receptor (PPAR). The PPAR activator rosiglitazone restored autophagy impaired by\n                    <jats:italic>fabp<\/jats:italic>\n                    knockdown and reduced\n                    <jats:italic>fabp<\/jats:italic>\n                    knockdown-induced increased A\u03b2 aggregation and cell death. Furthermore, knockdown of either\n                    <jats:italic>fabp<\/jats:italic>\n                    or\n                    <jats:italic>Eip75B<\/jats:italic>\n                    in the wing imaginal disc or adult fly brain reduced the expression of\n                    <jats:italic>Atg6<\/jats:italic>\n                    and\n                    <jats:italic>Atg8a<\/jats:italic>\n                    . Additionally, treatment of the\n                    <jats:italic>fabp<\/jats:italic>\n                    knockdown AD model flies with polyunsaturated fatty acids, such as docosahexaenoic acid or linoleic acid, partially alleviated cell death in the developing eye, restored impaired autophagy flux, reduced A\u03b2 aggregation, and attenuated A\u03b2-induced cell death. Our results suggest that\n                    <jats:italic>Drosophila<\/jats:italic>\n                    fabp plays an important role in maintaining protein homeostasis during aging and protects neurons from A\u03b2-induced cell death by enhancing autophagy through the PPAR pathway. These findings highlight the potential importance of neuronal FABP function in AD pathogenesis.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1011475","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T13:21:58Z","timestamp":1732022518000},"page":"e1011475","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Neuronal fatty acid-binding protein enhances autophagy and suppresses amyloid-\u03b2 pathology in a Drosophila model of Alzheimer\u2019s disease"],"prefix":"10.1371","volume":"20","author":[{"given":"Seokhui","family":"Jang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoungyun","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaejin","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Eun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyungi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunji","family":"Baek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3277-8269","authenticated-orcid":true,"given":"Kyoung Sang","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,19]]},"reference":[{"issue":"6","key":"pgen.1011475.ref001","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrd2589","article-title":"Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets","volume":"7","author":"M Furuhashi","year":"2008","journal-title":"Nat Rev Drug Discov"},{"issue":"12","key":"pgen.1011475.ref002","doi-asserted-by":"crossref","first-page":"158506","DOI":"10.1016\/j.bbalip.2019.08.002","article-title":"The ligand-mediated affinity of brain-type fatty acid-binding protein for membranes determines the directionality of lipophilic cargo transport","volume":"1864","author":"Y-Y Cheng","year":"2019","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"issue":"4","key":"pgen.1011475.ref003","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.cell.2020.07.027","article-title":"SnapShot: FABP functions","volume":"182","author":"B Li","year":"2020","journal-title":"Cell"},{"issue":"3","key":"pgen.1011475.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1479-7364-5-3-170","article-title":"The human fatty acid-binding protein family: evolutionary divergences and functions","volume":"5","author":"RL Smathers","year":"2011","journal-title":"Hum Genomics"},{"issue":"3","key":"pgen.1011475.ref005","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1620\/tjem.214.213","article-title":"Fatty acid binding protein: localization and functional significance in the brain","volume":"214","author":"Y. 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