{
  "abstract": "Neuronal Intranuclear Inclusion Disease (NIID) is caused by GGC repeat expansions in the 5' untranslated region of the notch 2 N-terminal like C (NOTCH2NLC) gene. An upstream open reading frame within the mutant transcript produces the NOTCH2NLC upstream open reading frame-derived polyglycine protein (uN2CpolyG) containing expanded polyglycine (polyG), which forms intranuclear inclusions. Although uN2CpolyG is thought to play a critical role in disease pathogenesis, the mechanisms underlying its toxicity and inclusion formation remain incompletely understood. In this study, we first expressed a pure GGC repeat encoding polyG in Neuro2a cells and identified aggregate-associated proteins by mass spectrometry. We then confirmed the formation of intracellular aggregates using both transient expression and drug-inducible expression systems for uN2CpolyG. Among the proteins identified by mass spectrometry, Calpain small subunit 1 (Capns1), the regulatory subunit of calpain, was found to be sequestered into uN2CpolyG aggregates. Notably, the N-terminus of Capns1 contains a glycine-rich sequence, which mediated its co-aggregation with uN2CpolyG. Furthermore, knockdown of Capns1 appeared to reduce the accumulation of uN2CpolyG aggregates. Collectively, these findings identify Capns1 as a potential modifier of NIID pathology.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Arisa Kubokawa"
    },
    {
      "name": "Ai Ohki"
    },
    {
      "name": "Risa Ono"
    },
    {
      "name": "Makoto Araki"
    },
    {
      "name": "Motoaki Yanaizu"
    },
    {
      "name": "Yoshihiro Kino"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2pkebvkn89cak.bib",
  "cited_by": 0,
  "doi": "10.1248/bpb.b26-00313",
  "fulltext_url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00313/_article",
  "id": "2pkebvkn89cak",
  "issns": [
    "1347-5215",
    "0918-6158"
  ],
  "landing_url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00313/_article",
  "language": null,
  "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": [
    [
      "jstage-journal",
      "medicine/pharmacology-toxicology"
    ],
    [
      "openalex",
      "2804|Genetic Neurodegenerative Diseases"
    ]
  ],
  "openalex": "W7204846113",
  "pdf_url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00313/_pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2pkebvkn89cak.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:32Z",
      "native_id": "10.1248/bpb.b26-00313",
      "source": "jstage",
      "url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00313/_article"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Genetic Neurodegenerative Diseases",
      "subfield": "neuroscience"
    }
  ],
  "title": "Sequestration of CAPNS1 into Polyglycine Aggregates in a Cellular Model of NOTCH2NLC Repeat Expansion",
  "title_text": "Sequestration of CAPNS1 into Polyglycine Aggregates in a Cellular Model of NOTCH2NLC Repeat Expansion",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:32Z",
  "url": "https://research.draconitic.com/paper/2pkebvkn89cak",
  "venue": "Biological and Pharmaceutical Bulletin",
  "versions": []
}