{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:44:18Z","timestamp":1791895458403,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BR1502\/21\u20101"],"award-info":[{"award-number":["BR1502\/21\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1286"],"award-info":[{"award-number":["SFB1286"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Protein homeostasis is essential for maintaining normal cellular function. However, protein homeostasis efficiency declines with age, leading to the accumulation of aberrant protein structures associated with neurodegenerative diseases such as Parkinson's disease (PD). PD is characterized by the aggregation of alpha\u2010synuclein (\u03b1Syn) into cytoplasmic inclusions. This process is accompanied by elevated phosphorylation at serine 129 (S129). The accumulation of \u03b1Syn into aggregates and their propagation disrupts key proteostasis pathways, including the ubiquitin\u2013proteasome system (UPS) or autophagy, contributing to cellular dysfunction and neuronal death. This study identified the proteasome activator Blm10 and its human ortholog PA200 as modulators of \u03b1Syn degradation and toxicity. The conserved Blm10\/PA200 protein plays a key role in regulating proteasome activity and assembly. The \u03b1Syn expression increases Blm10 protein stability through autophagy inhibition, in a manner dependent on \u03b1Syn phosphorylation at S129 in yeast. Overexpression of\n                    <jats:italic>BLM10<\/jats:italic>\n                    or\n                    <jats:italic>PA200<\/jats:italic>\n                    reduces \u03b1Syn aggregation and enhances \u03b1Syn turnover via activation of the 20S proteasome in yeast and mammalian cells. Blm10 and PA200\u2010capped 20S proteasomes efficiently degrade both monomeric as well as oligomeric \u03b1Syn in\u00a0vitro. Notably, capped proteasomes retain proteolytic activities in the presence of \u03b1Syn, indicating resistance to \u03b1Syn\u2010induced inhibition, in contrast to 20S or 26S proteasomes. These results reveal a distinct proteasome subtype that bypasses UPS impairment and restores proteolytic capacity under proteotoxic stress. Our findings establish Blm10\/PA200 as critical regulators of \u03b1Syn proteostasis and highlight its protective role in maintaining protein homeostasis and cell viability under conditions of \u03b1Syn toxicity.\n                  <\/jats:p>","DOI":"10.1111\/acel.70566","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T13:39:21Z","timestamp":1779975561000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Blm10\/\n                    <scp>PA200<\/scp>\n                    \u2010Activated\n                    <scp>20S<\/scp>\n                    Proteasomes Promote \u03b1\u2010Synuclein Degradation and Bypass Proteasome Inhibition in Parkinson's Disease Models"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8213-2608","authenticated-orcid":false,"given":"Tariq T.","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Genetics Institute of Microbiology and Genetics, University of G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Zhornyak","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Genetics Institute of Microbiology and Genetics, University of G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madiha","family":"Merghani","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurodegeneration, Centre for Biostructural Imaging of Neurodegeneration University Medical Centre G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zora","family":"Buschenlange","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurodegeneration, Centre for Biostructural Imaging of Neurodegeneration University Medical Centre G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Sakata","sequence":"additional","affiliation":[{"name":"Institute for Auditory Neuroscience University Medical Centre G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago F.","family":"Outeiro","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurodegeneration, Centre for Biostructural Imaging of Neurodegeneration University Medical Centre G\u00f6ttingen  G\u00f6ttingen Germany"},{"name":"German Centre for Neurodegenerative Diseases (DZNE)  G\u00f6ttingen Germany"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences Newcastle University  Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blagovesta","family":"Popova","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Genetics Institute of Microbiology and Genetics, University of G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-5626","authenticated-orcid":false,"given":"Gerhard H.","family":"Braus","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Genetics Institute of Microbiology and Genetics, University of G\u00f6ttingen  G\u00f6ttingen 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