{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:43:18Z","timestamp":1788493398972,"version":"build-2803163510"},"reference-count":66,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"crossref","award":["K132439"],"award-info":[{"award-number":["K132439"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"crossref","award":["PD 143786"],"award-info":[{"award-number":["PD 143786"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"crossref","award":["PD 137855"],"award-info":[{"award-number":["PD 137855"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University Excellence Fund of E\u00f6tv\u00f6s Lor\u00e1nd"},{"name":"National Research Excellence Program","award":["STARTING 150612"],"award-info":[{"award-number":["STARTING 150612"]}]},{"name":"Genetics Research Group HUN-REN-ELTE","award":["01062"],"award-info":[{"award-number":["01062"]}]},{"name":"DKOP-23 Doctoral Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund"},{"name":"NRDIO","award":["VEKOP-2.3.3-15-2016-00007"],"award-info":[{"award-number":["VEKOP-2.3.3-15-2016-00007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autophagy is a lysosome-mediated self-degradation process of eukaryotic cells which is critical for the elimination of cellular damage. Its capacity progressively declines with age, and this change can lead to the development of various neurodegenerative pathologies including Spinocerebellar ataxia type 1 (SCA1). SCA1 is mainly caused by mutations in the polyglutamine region of Ataxin 1 protein. In patients affected by the disease, Purkinje neurons of the cerebellum frequently undergo demise and eventually become lost. Here we tested whether two well-characterized autophagy-enhancing small molecules, AUTEN-67 and -99, which antagonize the autophagy complex Vps34 through blocking the myotubularin-related lipid phosphatase MTMR14\/EDTP, have the capacity to ameliorate SCA1 symptoms. We found that in a Drosophila model of SCA1, only AUTEN-67 exerts positive effects including improvement in climbing ability and extending life span. Based on these results, we hypothesized that the two compounds influence autophagy in the brain in a neuron-specific manner. Indeed, according to data we obtained, AUTEN-67 and -99 exhibit shared and unique functional domains in the Drosophila brain. AUTENs enhance autophagy in GABAergic and dopaminergic neurons. In addition, AUTEN-67 also affect autophagy in cholinergic neurons, while AUTEN-99 trigger the process in glutaminergic neurons and motoneurons. We also observed varying efficiencies between the two AUTENs among different subtypes of cultured hippocampal neurons of mice. These data suggest that the two compounds display neuron-specific differences in exerting autophagy-enhancing effects, and may lead to a better understanding of which types of neurons autophagy could potentially be activated to treat SCA1 in human patients.<\/jats:p>","DOI":"10.3390\/ijms262110443","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T09:16:07Z","timestamp":1761642967000},"page":"10443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative Analysis of Two Autophagy-Enhancing Small Molecules (AUTEN-67 and -99) in a Drosophila Model of Spinocerebellar Ataxia Type 1"],"prefix":"10.3390","volume":"26","author":[{"given":"T\u00edmea","family":"Burj\u00e1n","sequence":"first","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University (ELTE), 1053 Budapest, Hungary"},{"name":"Doctoral School of Biology, Institute of Biology, ELTE E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter S\u00e9t\u00e1ny 1\/C, 1053 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Aslam","sequence":"additional","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University (ELTE), 1053 Budapest, Hungary"},{"name":"Doctoral School of Biology, Institute of Biology, ELTE E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter S\u00e9t\u00e1ny 1\/C, 1053 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanni","family":"Keresztes","sequence":"additional","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University (ELTE), 1053 Budapest, Hungary"},{"name":"Doctoral School of Biology, Institute of Biology, ELTE E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter S\u00e9t\u00e1ny 1\/C, 1053 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1985-428X","authenticated-orcid":false,"given":"T\u00edmea","family":"Sigmond","sequence":"additional","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University (ELTE), 1053 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor A.","family":"Billes","sequence":"additional","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University (ELTE), 1053 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9553-3851","authenticated-orcid":false,"given":"Norbert","family":"Bencsik","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, E\u00f6tv\u00f6s Lor\u00e1nd University (ELTE), 1053 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9265-4236","authenticated-orcid":false,"given":"Katalin","family":"Schlett","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neurobiology, E\u00f6tv\u00f6s Lor\u00e1nd University (ELTE), 1053 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor","family":"Vellai","sequence":"additional","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University (ELTE), 1053 Budapest, Hungary"},{"name":"HUNREN-ELTE Genetic Research Group, 1097 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0632-9128","authenticated-orcid":false,"given":"Tibor","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Genetics, E\u00f6tv\u00f6s Lor\u00e1nd University (ELTE), 1053 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0076-6879(08)03230-8","article-title":"Autophagy in Caenorhabditis Elegans","volume":"451","author":"Sigmond","year":"2008","journal-title":"Methods Enzymol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ichimiya, T., Yamakawa, T., Hirano, T., Yokoyama, Y., Hayashi, Y., Hirayama, D., Wagatsuma, K., Itoi, T., and Nakase, H. 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