282474 20260105130521.0 pmc:PMC12635182 pmc 10.1038/s41531-025-01144-3 doi pmid:41266386 pmid DZNE-2025-01297 English 610 Lázaro, Diana F 0 Synphilin-1 modulates alpha-synuclein assembly, release and uptake. [London] 2025 Springer Nature article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1764763036_1689 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Alpha-synuclein (aSyn) is an intrinsically disordered protein involved in phase separation and several age-associated neurodegenerative disorders, including Parkinson's disease. However, its function and pathological role remain elusive. Here, we modeled different aSyn assemblies in living cells by exploiting its interaction with synphilin-1 (Sph1). We developed a model that reports on gel- and solid-like inclusions through coexpression of aSyn and Sph1. Distinct morphological differences emerged between VN-aSyn + aSyn-VC and VN-Sph1 + aSyn-VC assemblies, showing unique antibody recognition, proteinase K resistance, and protein mobilities. The VN-Sph1 + aSyn-VC interaction could be manipulated to alter inclusion size and number. These inclusions also contained lysosomes and AP-1 vesicles, aligning with observations in human brain tissue. Our study offers new insight into aSyn aggregation and release, highlighting the importance of Sph1 and other aSyn-interacting proteins in synucleinopathies, which involve diverse copathologies only now beginning to be understood. 352 - Disease Mechanisms (POF4-352) G:(DE-HGF)POF4-352 POF4-352 POF IV 0 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 1 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 2 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Amen, Triana 1 Gerhardt, Ellen 2 Song, Chengyuan 3 Burns, Ryan 4 Kruse, Niels P:(DE-HGF)0 5 Santos, Patrícia I 6 Milovanovic, Dragomir P:(DE-2719)9000670 7 Höglinger, Günter P:(DE-2719)2811373 8 Mollenhauer, Brit P:(DE-2719)9001340 9 Luk, Kelvin C 10 Lee, Virginia My- 11 Outeiro, Tiago P:(DE-2719)2814138 12 Last author 10.1038/s41531-025-01144-3 Vol. 11, no. 1, p. 326 PERI:(DE-600)2819218-7 1 326 npj Parkinson's Disease 11 2025 2373-8057 OpenAccess http://pub.dzne.de/record/282474/files/DZNE-2025-01297.pdf OpenAccess pdfa http://pub.dzne.de/record/282474/files/DZNE-2025-01297.pdf?subformat=pdfa oai:pub.dzne.de:282474 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 5 P:(DE-HGF)0 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 7 P:(DE-2719)9000670 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 8 P:(DE-2719)2811373 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 9 P:(DE-2719)9001340 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 12 P:(DE-2719)2814138 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Mechanisms 0 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 1 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 2 2025 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2024-12-11 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2024-12-11 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2024-12-11 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC JCR StatID:(DE-HGF)0100 StatID NPJ PARKINSONS DIS : 2022 2024-12-11 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2024-04-10T15:43:48Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2024-04-10T15:43:48Z WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2024-12-11 Fees StatID:(DE-HGF)0700 StatID 2024-12-11 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2024-12-11 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Anonymous peer review 2024-04-10T15:43:48Z Article Processing Charges StatID:(DE-HGF)0561 StatID 2024-12-11 IF >= 5 StatID:(DE-HGF)9905 StatID NPJ PARKINSONS DIS : 2022 2024-12-11 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2024-12-11 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2024-12-11 I:(DE-2719)1410002 AG Fischer Epigenetics and Systems Medicine in Neurodegenerative Diseases 0 I:(DE-2719)1813002 AG Milovanovic (Berlin) Molecular Neuroscience 1 I:(DE-2719)1111015 Clinical Research (Munich) Clinical Research (Munich) 2 journal VDB UNRESTRICTED I:(DE-2719)1410002 I:(DE-2719)1813002 I:(DE-2719)1111015 FullTexts