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Thus, tremendous efforts are being made to develop strategies to prevent or inhibit \u03b1\u2010Syn aggregation. Here, we genetically engineered fission yeast to express human \u03b1\u2010Syn C\u2010terminally fused to green fluorescent protein (GFP) at low and high levels. \u03b1\u2010Syn was localized at the cell tips and septa at low\u2010level expression. At high\u2010level expression, \u03b1\u2010Syn was observed to form cytoplasmic aggregates. Notably, rapamycin, a natural product that allosterically inhibits the mammalian target of rapamycin (mTOR) by forming a complex with FKBP12, and Torin1, a synthetic mTOR inhibitor that blocks ATP binding to mTOR, markedly reduced the number of cells harboring \u03b1\u2010Syn aggregates. These mTOR inhibitors abrogate \u03b1\u2010Syn aggregation without affecting \u03b1\u2010Syn expression levels. Rapamycin, but not Torin1, failed to reduce \u03b1\u2010Syn aggregation in the deletion cells of\n                    <jats:italic>fkh1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    , encoding FKBP12, indicating the requirement of FKBP12 for rapamycin\u2010mediated inhibition of \u03b1\u2010Syn aggregation. Importantly, the effect of rapamycin was also observed in the cells lacking\n                    <jats:italic>atg1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    , a key regulator of autophagy. Collectively, rapamycin abrogates human \u03b1\u2010Syn aggregation expressed in fission yeast via an autophagy\u2010independent mechanism mediated by FKBP12.\n                  <\/jats:p>","DOI":"10.1111\/gtc.13185","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T23:28:41Z","timestamp":1734564521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rapamycin Abrogates Aggregation of Human \u03b1\u2010Synuclein Expressed in Fission Yeast via an Autophagy\u2010Independent Mechanism"],"prefix":"10.1111","volume":"30","author":[{"given":"Yoshitaka","family":"Sugimoto","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Higashiosaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teruaki","family":"Takasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Higashiosaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuga","family":"Yamada","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Higashiosaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Kurosaki","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Higashiosaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonari","family":"Yamane","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Higashiosaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6946-0935","authenticated-orcid":false,"given":"Reiko","family":"Sugiura","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacogenomics, Department of Pharmaceutical Sciences Kindai University  Higashiosaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","DOI":"10.1002\/brb3.2628","article-title":"Modeling Parkinson's Disease\u2010Related Symptoms in Alpha\u2010Synuclein Overexpressing Mice","volume":"12","author":"Aniszewska A.","year":"2022","journal-title":"Brain and Behavior: A Cognitive Neuroscience Perspective"},{"key":"e_1_2_8_3_1","first-page":"879","article-title":"Aggregation of Alpha\u2010Synuclein in Lewy Bodies of Sporadic Parkinson's Disease and Dementia With Lewy Bodies","volume":"152","author":"Baba M.","year":"1998","journal-title":"American Journal of Pathology"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/35072550"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.09.004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.4.799-813.2005"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:28:2:179"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)90417-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2014.117"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.66.4.579-591.2002"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/35006074"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00299"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.5402\/2011\/521847"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1604645113"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.01.017"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32542-3"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/35081564"},{"key":"e_1_2_8_18_1","first-page":"289","article-title":"The Strong ADH1 Promoter Stimulates Mitotic and Meiotic Recombination at the ADE6 Gene of Schizosaccharomyces Pombe","volume":"11","author":"Grimm C.","year":"1991","journal-title":"Molecular and Cellular Biology"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12545"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000027"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.120.000133"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73939"},{"key":"e_1_2_8_23_1","volume-title":"Animal Models of Parkinson's Disease","author":"Konnova E. 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