{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mahul-Mellier AL"],"funding":["Fondation Bru","EU-ITN","Swedish Research Council","Reta Lila Weston Institute for Neurological Studies and the Medical Research Council UK","National Institute for Health Research University College London Hospitals Biomedical Research Centre","EU Joint Programme – Neurodegenerative Disease Research","the Multiple System Atrophy Coalition","Multiple System Atrophy Trust","UCB","Karin & Sten Mortstedt CBD Solutions","NNSF","École Polytechnique Fédérale de Lausanne","Fund Sophia, managed by the King Baudouin Foundation","Joint Program for Neurodegenerative Diseases (JPND) from the UK Medical Research Council","EU Joint Programme - Neurodegenerative Disease Research"],"pagination":["261"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12381302"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(1)"],"pubmed_abstract":["Alpha-synuclein (aSyn) post-translational modifications (PTM), especially phosphorylation at serine 129 and C-terminal truncations, are highly enriched in Lewy bodies (LB), Lewy neurites, and other pathological aggregates in Parkinson's disease and synucleinopathies. However, the precise role of these PTM in pathology formation, neurodegeneration, and pathology spreading remains unclear. Here, we systematically investigated the role of post-fibrillization C-terminal aSyn truncations in regulating uptake, processing, seeding, and LB-like inclusion formation using a neuronal seeding model that recapitulates LB formation and neurodegeneration. We show that C-terminal cleavage of aSyn fibrils occurs rapidly post exogenous fibril internalization and during intracellular LB-like inclusion format"],"journal":["NPJ Parkinson's disease"],"pubmed_title":["Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation."],"pmcid":["PMC12381302"],"funding_grant_id":["aSynProtec, REfrAME","NNSF-81430025","BRU_PARKINSON","Syndegen"],"pubmed_authors":["Haikal C","Maharjan N","Ait-Bouziad N","Knott G","Novello S","Jagannath S","Vingill S","Downey P","Altay MF","Mairet-Coello G","Citron M","Wade-Martins R","Weerens L","Mahul-Mellier AL","Hamelin R","Michel A","Limorenko G","Li JY","Strand C","Croisier M","Chiki A","Ricci J","Holton J","Jasiqi Y","Lashuel HA"],"additional_accession":[]},"is_claimable":false,"name":"Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation.","description":"Alpha-synuclein (aSyn) post-translational modifications (PTM), especially phosphorylation at serine 129 and C-terminal truncations, are highly enriched in Lewy bodies (LB), Lewy neurites, and other pathological aggregates in Parkinson's disease and synucleinopathies. However, the precise role of these PTM in pathology formation, neurodegeneration, and pathology spreading remains unclear. Here, we systematically investigated the role of post-fibrillization C-terminal aSyn truncations in regulating uptake, processing, seeding, and LB-like inclusion formation using a neuronal seeding model that recapitulates LB formation and neurodegeneration. We show that C-terminal cleavage of aSyn fibrils occurs rapidly post exogenous fibril internalization and during intracellular LB-like inclusion format","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-29T19:28:09.297Z","creation":"2026-04-08T05:47:27.993Z"},"accession":"S-EPMC12381302","cross_references":{"pubmed":["40858624"],"doi":["10.1038/s41531-025-01084-y"]}}