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Previous studies demonstrate how a limited number of transcription factors (TFs) can increase autophagy. However, this knowledge has not resulted in translation into therapy, thus, to gain understanding of more suitable targets, we utilized a systems biology approach. We induced autophagy by amino acid starvation and mTOR inhibition in HeLa, HEK 293 and SH-SY5Y cells and measured temporal gene expression using RNA-seq. We observed 456 differentially expressed genes due to starvation and 285 genes due to mTOR inhibition (P\n                    <jats:sub>FDR<\/jats:sub>\n                    \u2009&lt;\u20090.05 in every cell line). Pathway analyses implicated Alzheimer\u2019s and Parkinson\u2019s diseases (P\n                    <jats:sub>FDR<\/jats:sub>\n                    \u2009\u2264\u20090.024 in SH-SY5Y and HeLa) and amyotrophic lateral sclerosis (ALS, P\n                    <jats:sub>FDR<\/jats:sub>\n                    \u2009&lt;\u20090.05 in mTOR inhibition experiments). Differential expression of the Senataxin (SETX) target gene set was predicted to activate multiple neurodegenerative pathways (P\n                    <jats:sub>FDR<\/jats:sub>\n                    \u2009\u2264\u20090.04). In the SH-SY5Y cells of neuronal origin, the E2F transcription family was predicted to activate Alzheimer\u2019s disease pathway (P\n                    <jats:sub>FDR<\/jats:sub>\n                    \u2009\u2264\u20090.0065). These exploratory analyses suggest that SETX and E2F may mediate transcriptional regulation of autophagy and further investigations into their possible role in neuro-degeneration are warranted.\n                  <\/jats:p>","DOI":"10.1038\/s41598-022-21617-2","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T08:06:36Z","timestamp":1666339596000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Transcriptional targets of senataxin and E2 promoter binding factors are associated with neuro-degenerative pathways during increased autophagic flux"],"prefix":"10.1038","volume":"12","author":[{"given":"Aaron E.","family":"Casey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne K.","family":"Hein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Sargeant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Pederson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ville-Petteri","family":"M\u00e4kinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"21617_CR1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.014175","volume":"9","author":"R Du","year":"2020","unstructured":"Du, R. et al. 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