{
  "abstract": "Abnormal -synuclein aggregation is the defining feature of Parkinson's disease (PD) and related synucleinopathies. Rare disease-causing alpha-synuclein mutations either accelerate or slow fibrillization in vitro, however their effects in vivo are less well understood. Interestingly, the A53E mutation slows fibrillization in vitro but causes a more virulent form of PD. We use an in vivo model to examine the aggregation dynamics of disease-causing A53E and E46K alpha-synuclein mutations. Fluorescence recovery after photobleaching within presynaptic terminals shows that A53E-alpha-synuclein is significantly more mobile than E46K- or wild-type (WT)-alpha-synuclein. Longitudinal analysis in vivo reveals that E46K- and WT-alpha-synuclein become progressively less mobile over days, while A53E maintains high mobility, suggesting delayed progression toward aggregated states. We also find that A53E-alpha-synuclein lacks detectable disease-relevant phosphorylation at serine-129, unlike E46K-and WT-alpha-synuclein. To mechanistically test whether this unique lack of phosphorylation drives its high mobility, we genetically modified A53E-alpha-synuclein to mimic S129 phosphorylation, and show that this manipulation indeed decreases its mobility, directly implicating the phosphorylation status of this residue in mobility.",
  "abstract_shown": true,
  "affiliations": [
    "Lewis & Clark College"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "W. L. Irving"
    },
    {
      "name": "S. Meredith-Andrews"
    },
    {
      "name": "K. T. Nguyen"
    },
    {
      "name": "K. L. Schainker"
    },
    {
      "name": "N. L. Brockway"
    },
    {
      "name": "V. K. Unni"
    },
    {
      "affs": [
        0
      ],
      "name": "T. A. Weissman"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/86cwkfyg8fsx6.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.29.762882",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.29.762882v1.full",
  "id": "86cwkfyg8fsx6",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.29.762882v1",
  "language": "en",
  "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"
    ],
    [
      "heading",
      "Article"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.29.762882v1.full.pdf",
  "pmcid": "PMC13734114",
  "pmid": "42990431",
  "published": "2026-10-29",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/86cwkfyg8fsx6.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:21:18Z",
      "native_id": "10.64898/2026.10.29.762882",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.29.762882v1"
    },
    {
      "first_seen": "2026-11-08T12:23:45Z",
      "native_id": "PMC13734114",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.29.762882"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "The Parkinson's disease-associated A53E mutation decreases alpha-synuclein aggregation and phosphorylation in vivo",
  "title_text": "The Parkinson's disease-associated A53E mutation decreases alpha-synuclein aggregation and phosphorylation in vivo",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:45Z",
  "url": "https://research.draconitic.com/paper/86cwkfyg8fsx6",
  "venue": "bioRxiv",
  "versions": []
}