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However, key regulators of these pleotropic traits have yet to be identified. Here, we discovered a novel long non-coding RNA (lncRNA),\n                  <jats:italic>FAM151B-DT<\/jats:italic>\n                  , that is reduced in a stem cell model of frontotemporal dementia with tau inclusions (FTLD-tau) and in brains from FTLD-tau, progressive supranuclear palsy, Alzheimer\u2019s disease, and Parkinson\u2019s disease patients. We show that silencing\n                  <jats:italic>FAM151B-DT in vitro<\/jats:italic>\n                  is sufficient to enhance tau aggregation. To begin to understand the mechanism by which\n                  <jats:italic>FAM151B-DT<\/jats:italic>\n                  mediates tau aggregation and contributes to several neurodegenerative diseases, we deeply characterized this novel lncRNA and found that\n                  <jats:italic>FAM151B-DT<\/jats:italic>\n                  resides in the cytoplasm where it interacts with tau, \u03b1-synuclein, HSC70, and other proteins enriched in protein homeostasis. When silenced,\n                  <jats:italic>FAM151B-DT<\/jats:italic>\n                  blocks autophagy, leading to the accumulation of tau and \u03b1-synuclein. Importantly, we discovered that increasing\n                  <jats:italic>FAM151B-DT<\/jats:italic>\n                  expression is sufficient to promote autophagic flux, reduce phospho-tau and \u03b1-synuclein, and reduce tau aggregation. Overall, these findings pave the way for further exploration of\n                  <jats:italic>FAM151B-DT<\/jats:italic>\n                  as a promising molecular target for several neurodegenerative diseases.\n                <\/jats:p>","DOI":"10.1101\/2025.01.22.25320997","type":"posted-content","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T14:15:17Z","timestamp":1737728117000},"source":"Crossref","is-referenced-by-count":1,"title":["A novel lncRNA FAM151B-DT regulates autophagy and degradation of aggregation prone proteins"],"prefix":"10.64898","author":[{"given":"Arun","family":"Renganathan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Minaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Broder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Alfradique-Dunham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Moritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reshma","family":"Bhagat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Marsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Verbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Galasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Starr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Agard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Cruchaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-5547","authenticated-orcid":false,"given":"Celeste M.","family":"Karch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025012623502390000_2025.01.22.25320997v1.1","first-page":"1083","article-title":"[Tauopathies : From molecule to therapy]","volume":"89","year":"2018","journal-title":"Nervenarzt"},{"key":"2025012623502390000_2025.01.22.25320997v1.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.1121"},{"key":"2025012623502390000_2025.01.22.25320997v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00533-z"},{"key":"2025012623502390000_2025.01.22.25320997v1.4","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/s41398-022-02274-5","article-title":"Defective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration","volume":"12","year":"2022","journal-title":"Transl Psychiatry"},{"key":"2025012623502390000_2025.01.22.25320997v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22501-9"},{"key":"2025012623502390000_2025.01.22.25320997v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.01.017"},{"key":"2025012623502390000_2025.01.22.25320997v1.7","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021108863"},{"key":"2025012623502390000_2025.01.22.25320997v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.02.008"},{"key":"2025012623502390000_2025.01.22.25320997v1.9","doi-asserted-by":"crossref","unstructured":"Kumar A , et al. 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