{
  "abstract": ", age-related macular degeneration, glaucoma). A common feature of neurodegeneration is the progressive accumulation of amyloidogenic proteins such as beta-amyloid and tau protein (MAPT gene). There is compelling evidence that the aggregation propensity of tau protein is regulated by post-synthetic modifications including phosphorylation and ubiquitylation. These alterations are gaining increasing pathological relevance not only for brain tauopathies but also for the retinal/optic nerve degenerative diseases. In this regard, site-specific mono-ubiquitylated (Ub) tau proteoforms, have been recently identified in neurodegenerative brains. In this work, the cleavage patterns of the uncapped 20S proteasome acting on mono-Ub regio-isomers of tauK18, which covers the 4RD domain, have been unveiled by using SpectraSage, a novel proteomics software conceived for the MS1 identification of complex branched peptide and here introduced for the first time. Ub position was found to affect regio-isomers susceptibility to proteolysis and unexpectedly long Ub-tauK18 branched peptides have been identified, proving distinct catalytic preferences. These findings show that the 20S digests mono-Ub proteins through specific enzymatic mechanisms and the implications of the latter on neurodegeneration are discussed.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "Gabriele Antonio Zingale"
    },
    {
      "name": "Irene Pandino"
    },
    {
      "name": "Daniele Trivellato"
    },
    {
      "name": "Dario Cavaterra"
    },
    {
      "name": "Francesca Munari"
    },
    {
      "name": "Giuseppe Grasso"
    },
    {
      "name": "Peter Bell"
    },
    {
      "name": "Francesco Oddone"
    },
    {
      "name": "Alessio Bocedi"
    },
    {
      "name": "Massimiliano Coletta"
    },
    {
      "name": "Michael Assfalg"
    },
    {
      "name": "Mariapina d'Onofrio"
    },
    {
      "name": "Grazia Raffaella Tundo"
    },
    {
      "name": "Diego Sbardella"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bb9xtk2hpqgda.bib",
  "cited_by": 2,
  "doi": "10.1039/d5sc04240b",
  "fulltext_url": null,
  "id": "bb9xtk2hpqgda",
  "issns": [
    "2041-6520",
    "2041-6539"
  ],
  "landing_url": "https://hal.science/hal-05782945v1",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bbm"
    ],
    [
      "hal",
      "1.sdv.mhep"
    ],
    [
      "hal",
      "2.sdv.bbm.gtp"
    ],
    [
      "openalex",
      "1312|Ubiquitin and proteasome pathways"
    ]
  ],
  "openalex": "W4413371619",
  "pdf_url": "https://pubs.rsc.org/en/content/articlepdf/2025/sc/d5sc04240b",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": "The Royal Society of Chemistry",
  "ris": "https://research.draconitic.com/paper/bb9xtk2hpqgda.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:50Z",
      "native_id": "hal-05782945",
      "source": "hal",
      "url": "https://hal.science/hal-05782945v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "hal:2.sdv.bbm.gtp",
      "subfield": "proteomics-metabolomics"
    },
    {
      "field": "biology",
      "origin": "hal:0.sdv",
      "subfield": "general"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.mhep",
      "subfield": "general"
    }
  ],
  "title": "SpectraSage unveils specific proteolytic patterns of 20S on mono-ubiquitylated Tau proteoforms involved in neurodegeneration",
  "title_text": "SpectraSage unveils specific proteolytic patterns of 20S on mono-ubiquitylated Tau proteoforms involved in neurodegeneration",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:50Z",
  "url": "https://research.draconitic.com/paper/bb9xtk2hpqgda",
  "venue": "Chemical Science",
  "versions": []
}