{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:05:07Z","timestamp":1789758307124,"version":"4.0.1"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Aggregation of the protein \u03b1-Synuclein (\u03b1Syn) is a hallmark of Parkinson\u2019s disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy, and alleviating the extent of \u03b1Syn pathology is an attractive strategy against neurodegeneration. The engineered binding protein \u03b2-wrapin AS69 binds monomeric \u03b1Syn. AS69 reduces primary and secondary nucleation as well as fibril elongation in vitro. It also mitigates aSyn pathology in a mouse model based on intrastriatal injection of aSyn pre-formed fibrils (PFFs). Since the PFF-based model does not represent all aspects of PD, we tested here whether AS69 can reduce neurodegeneration resulting from \u03b1Syn overexpression. Human A53T-\u03b1Syn was overexpressed in the mouse Substantia nigra (SN) by using recombinant adeno-associated viral vector (rAAV). AS69 was also expressed by rAAV transduction. Behavioral tests and immunofluorescence staining were used as outcomes. Transduction with rAAV-\u03b1Syn resulted in \u03b1Syn pathology as reported by phospho-\u03b1Syn staining and caused degeneration of dopaminergic neurons in the SN. The co-expression of rAAV-AS69 did not reduce \u03b1Syn pathology or the degeneration of dopaminergic neurons. We conclude that \u03b1Syn monomer binding by rAAV-AS69 was insufficient to protect from aSyn pathology resulting from \u03b1Syn overexpression.<\/jats:p>","DOI":"10.3390\/biom14070756","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T05:11:39Z","timestamp":1719465099000},"page":"756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of the Effect of \u03b2-Wrapin AS69 in a Mouse Model Based on Alpha-Synuclein Overexpression"],"prefix":"10.3390","volume":"14","author":[{"given":"Lennart","family":"H\u00f6fs","sequence":"first","affiliation":[{"name":"Department of Neurology, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8332-2145","authenticated-orcid":false,"given":"David","family":"Gei\u00dfler-L\u00f6sch","sequence":"additional","affiliation":[{"name":"Department of Neurology, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristof M.","family":"Wunderlich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2629-2131","authenticated-orcid":false,"given":"Eva M.","family":"Szeg\u00f6","sequence":"additional","affiliation":[{"name":"Department of Neurology, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Van den Haute","sequence":"additional","affiliation":[{"name":"Leuven Viral Vector Core, KU Leuven, 3000 Leuven, Belgium"},{"name":"Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Baekelandt","sequence":"additional","affiliation":[{"name":"Leuven Viral Vector Core, KU Leuven, 3000 Leuven, Belgium"},{"name":"Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven Brain Institute, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4301-5416","authenticated-orcid":false,"given":"Wolfgang","family":"Hoyer","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physikalische Biologie, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Institute of Biological Information Processing (IBI-7), Forschungszentrum J\u00fclich GmbH, 52428 J\u00fclich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-526X","authenticated-orcid":false,"given":"Bj\u00f6rn H.","family":"Falkenburger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1002\/mds.27115","article-title":"Past, Present, and Future of Parkinson\u2019s Disease: A Special Essay on the 200th Anniversary of the Shaking Palsy","volume":"32","author":"Obeso","year":"2017","journal-title":"Mov. 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