{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T21:16:06Z","timestamp":1788038166603,"version":"build-2784847793"},"posted":{"date-parts":[[2026,8,27]]},"group-title":"Neuroscience","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"name":"DFG","award":["eBer-23-17831"],"award-info":[{"award-number":["eBer-23-17831"]}]},{"name":"DFG","award":["INST 192\/574-1 FUGG"],"award-info":[{"award-number":["INST 192\/574-1 FUGG"]}]},{"name":"DFG","award":["PO732"],"award-info":[{"award-number":["PO732"]}]},{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative e.V.","doi-asserted-by":"crossref","award":["21043"],"award-info":[{"award-number":["21043"]}],"id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer Association","doi-asserted-by":"crossref","award":["AARG-23-1141447"],"award-info":[{"award-number":["AARG-23-1141447"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MWK Europa-Programm","award":["15-76251-1-22\/26"],"award-info":[{"award-number":["15-76251-1-22\/26"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Tauopathies are devastating neurodegenerative disorders characterized by Tau hyperphosphorylation, neurofibrillary tangle (NFT) formation, neuronal dysfunction, and cognitive decline.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Here, we establish a new Drosophila tauopathy model expressing eGFP-tagged human Tau\n                    <jats:sup>WT<\/jats:sup>\n                    or the disease-associated Tau\n                    <jats:sup>P301L<\/jats:sup>\n                    variant in the nervous system.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Tau\n                    <jats:sup>P301L<\/jats:sup>\n                    expression recapitulates key pathological and behavioral hallmarks of tauopathy, including elevated Tau hyperphosphorylation, accumulation of NFT-like, pTau-positive assemblies\n                    <jats:italic>in vivo<\/jats:italic>\n                    , reduced lifespan, hyperactivity, sleep loss, progressive locomotor decline, and age-dependent brain degeneration. Strikingly, Tau\n                    <jats:sup>P301L<\/jats:sup>\n                    also disrupts the architecture of the mushroom body, a learning- and memory-related circuit in Drosophila, revealing an early disruption of neural circuit formation that is distinct from adult neurodegenerative phenotypes. We further show that suppression of serotonin 5-HT7R-CDK5 signaling pathway, either by genetic knockdown or pharmacological inhibition with inverse agonist, rescues Tau-induced behavioral and anatomical phenotypes.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    These findings identify 5-HT7R signaling as a conserved and druggable modifier of Tau toxicity and establish this model as a powerful\n                    <jats:italic>in vivo<\/jats:italic>\n                    platform for mechanistic studies and therapeutic discovery in tauopathies.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.24.746720","type":"posted-content","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T01:05:50Z","timestamp":1787879150000},"source":"Crossref","is-referenced-by-count":0,"title":["A conserved serotonin receptor pathway is a druggable modifier of Tau pathology, neural circuit formation and neurodegeneration"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0891-8504","authenticated-orcid":false,"given":"Mariana I.","family":"Tsap","sequence":"first","affiliation":[{"name":"Institute of Cell Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6523-9456","authenticated-orcid":false,"given":"Valeriya V.","family":"Navrotska","sequence":"additional","affiliation":[{"name":"Institute of Cell Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany"},{"name":"Institute of Neurophysiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5064-6382","authenticated-orcid":false,"given":"Josephine","family":"Labus","sequence":"additional","affiliation":[{"name":"Institute of Neurophysiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4570-5130","authenticated-orcid":false,"given":"Evgeni","family":"Ponimaskin","sequence":"additional","affiliation":[{"name":"Institute of Neurophysiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8730-5744","authenticated-orcid":false,"given":"Andriy S.","family":"Yatsenko","sequence":"additional","affiliation":[{"name":"Institute of Cell Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3855-0345","authenticated-orcid":false,"given":"Halyna R.","family":"Shcherbata","sequence":"additional","affiliation":[{"name":"Institute of Cell Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany"},{"name":"Mount Desert Island Biological Laboratory, 159 Old Bar Harbor Road, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026082913350464000_2026.08.24.746720v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00753-9"},{"key":"2026082913350464000_2026.08.24.746720v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.11.030"},{"key":"2026082913350464000_2026.08.24.746720v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-025-01575-9"},{"key":"2026082913350464000_2026.08.24.746720v1.4","doi-asserted-by":"crossref","unstructured":"Silva MC , Haggarty SJ . 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