{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:52:34Z","timestamp":1760233954594,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Huntington\u2019s disease (HD) is a monogenetic neurodegenerative disorder characterized by the accumulation of polyglutamine-expanded huntingtin (mHTT). There is currently no cure, and therefore disease-slowing remedies are sought to alleviate symptoms of the multifaceted disorder. Encouraging findings in Alzheimer\u2019s and Parkinson\u2019s disease on alpha-2 adrenoceptor (\u03b12-AR) inhibition have shown neuroprotective and aggregation-reducing effects in cell and animal models. Here, we analyzed the effect of beditin, a novel \u03b12- adrenoceptor (AR) antagonist, on cell viability and mHTT protein levels in cell models of HD using Western blot, time-resolved Foerster resonance energy transfer (TR-FRET), lactate dehydrogenase (LDH) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) cytotoxicity assays. Beditin decreases cytotoxicity, as measured by TUNEL staining and LDH release, in a neuronal progenitor cell model (STHdh cells) of HD and decreases the aggregation propensity of HTT exon 1 fragments in an overexpression model using human embryonic kidney (HEK) 293T cells. \u03b12-AR is a promising therapeutic target for further characterization in HD models. Our data allow us to suggest beditin as a valuable candidate for the pharmaceutical manipulation of \u03b12-AR, as it is capable of modulating neuronal cell survival and the level of mHTT.<\/jats:p>","DOI":"10.3390\/ph14030257","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T23:52:06Z","timestamp":1615765926000},"page":"257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Novel Alpha-2 Adrenoceptor Inhibitor Beditin Reduces Cytotoxicity and Huntingtin Aggregates in Cell Models of Huntington\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6669-9676","authenticated-orcid":false,"given":"Elisabeth","family":"Singer","sequence":"first","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Calwerstrasse 7, 72076 Tuebingen, Germany"},{"name":"Centre for Rare Diseases (ZSE), University of Tuebingen, Calwerstrasse 7, 72076 Tuebingen, Germany"},{"name":"Department of Human Genetics, Ruhr University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilit","family":"Hunanyan","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Yerevan State Medical University, Yerevan 0025, Armenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magda M.","family":"Melkonyan","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Yerevan State Medical University, Yerevan 0025, Armenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3758-1569","authenticated-orcid":false,"given":"Jonasz J.","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Calwerstrasse 7, 72076 Tuebingen, Germany"},{"name":"Centre for Rare Diseases (ZSE), University of Tuebingen, Calwerstrasse 7, 72076 Tuebingen, Germany"},{"name":"Department of Human Genetics, Ruhr University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4130-8477","authenticated-orcid":false,"given":"Lusine","family":"Danielyan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, University Hospital of Tuebingen, 72076 Tuebingen, Germany"},{"name":"Department of Biochemistry and Neuroscience Laboratory, Yerevan State Medical University, Yerevan 0025, Armenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6139-788X","authenticated-orcid":false,"given":"Huu Phuc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Ruhr University Bochum, Universitaetsstrasse 150, 44801 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"The Huntington\u2019s Disease Collaborative Research Group (1993). 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