{
  "abstract": "Understanding how soluble monomeric alpha-synuclein transitions into pathological alpha-synuclein (Lewy bodies) has remained a central challenge in neurodegeneration. Existing models, largely based on treating cells and animals with pre-formed alpha-synuclein fibrils cannot account for the emergence of the first inclusion without pre-existing seeds. Here, we combine in vitro reconstitutions, computational modeling and a minimal cellular system to show that phase separation of alpha-synuclein with an interacting scaffold can recapitulate Lewy body-like structures. An unbiased proteomics screen, live-cell imaging, correlative light-electron microscopy, and soft X-ray tomography show that Lewy body-like structures are associated with redistribution of actin and membrane-bound organelles, with mitochondria accumulating at their periphery in an actin-dependent manner. Structural analyses further indicate that alpha-synuclein condensates provide local environments in which the insoluble beta-sheets can form. Together, these findings support a seed-independent trajectory from soluble alpha-synuclein through condensation and progressive immobilization to Lewy body-like assemblies and, subsequently, insoluble beta-sheet fibrils. This framework offers a new mechanistic route for understanding the disease progression and promises to guide the design of innovative therapeutic interventions.",
  "abstract_shown": true,
  "affiliations": [
    "Charite - Berlin University Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 42,
  "authors": [
    {
      "name": "R. Sansevrino"
    },
    {
      "name": "A. Korobeinikov"
    },
    {
      "name": "J.-H. Chen"
    },
    {
      "name": "C. Hoffmann"
    },
    {
      "name": "H. Le Roy"
    },
    {
      "name": "K. M. Ruff"
    },
    {
      "name": "A. Major"
    },
    {
      "name": "A. Nayak"
    },
    {
      "name": "P. Brosius"
    },
    {
      "name": "A. Ekman"
    },
    {
      "name": "S. He"
    },
    {
      "name": "M. Chen"
    },
    {
      "name": "J. Jackson"
    },
    {
      "name": "G. Aguilar Perez"
    },
    {
      "name": "H. Wang"
    },
    {
      "name": "J. V. Tromm"
    },
    {
      "name": "G. Schneider"
    },
    {
      "name": "K. Lau"
    },
    {
      "name": "K. Textoris-Taube"
    },
    {
      "name": "L. R. Sinn"
    },
    {
      "name": "R. de Boer"
    },
    {
      "name": "L. T. Hofstede"
    },
    {
      "name": "J. Franz"
    },
    {
      "name": "M. A. Le Gros"
    },
    {
      "name": "S. O. Rizzoli"
    },
    {
      "name": "T. F. Outeiro"
    },
    {
      "name": "P. De Los Rios"
    },
    {
      "name": "V. Demichev"
    },
    {
      "name": "M. Muelleder"
    },
    {
      "name": "M. Ralser"
    },
    {
      "name": "D. Schmitz"
    },
    {
      "name": "D. Bano"
    },
    {
      "name": "G. van den Bogaart"
    },
    {
      "name": "Y. Dai"
    },
    {
      "name": "A. J. Espay"
    },
    {
      "name": "B. Eickholt"
    },
    {
      "name": "C. Stadelmann"
    },
    {
      "name": "P. P. Gopal"
    },
    {
      "name": "R. V. Pappu"
    },
    {
      "name": "T. Salditt"
    },
    {
      "name": "C. Larabell"
    },
    {
      "affs": [
        0
      ],
      "name": "D. Milovanovic"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b2nty36xks44t.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.09.757996",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757996v1.full",
  "id": "b2nty36xks44t",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757996v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7222178611",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757996v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b2nty36xks44t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:56Z",
      "native_id": "10.64898/2026.10.09.757996",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757996v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Reverse engineering Lewy bodies suggests alpha-synuclein pathology as condensatopathy",
  "title_text": "Reverse engineering Lewy bodies suggests alpha-synuclein pathology as condensatopathy",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:56Z",
  "url": "https://research.draconitic.com/paper/b2nty36xks44t",
  "venue": "bioRxiv",
  "versions": []
}