{
  "abstract": "Neurofibromatosis type 1 (NF1) predisposes to peripheral nerve sheath tumors arising from Schwann-lineage cells with biallelic NF1 loss and remains in need of biologically informed strategies compatible with chronic disease management. Curcumin has attracted interest in NF1, but its effects in disease-relevant cells remain unclear. Here, we investigated curcumin responses in patient-derived NF1-deficient Schwann cells. Curcumin induced the progressive accumulation of cytoplasmic vacuoles resembling those elicited by a reference methuosis inducer, without prominent evidence of canonical apoptotic features. Vacuolization was associated with impaired long-term clonogenic recovery, indicating a durable loss of proliferative fitness. NF1-deficient Schwann cells displayed lower levels of NRF2, thioredoxin, and SOD1 than NF1-proficient cells under basal and curcumin-treated conditions, defining a distinct NF1-associated antioxidant-response context. Consistent with a functionally relevant redox-sensitive component, N-acetylcysteine pretreatment reduced curcumin-induced vacuolization to near-basal levels and substantially improved clonogenic recovery after drug washout. NF1-proficient Schwann cells showed an attenuated vacuolizing response, whereas acute NF1 silencing in hTERT RPE-1 cells enhanced curcumin-induced vacuolization in an independent cellular background. Together, these findings identify an NAC-sensitive vacuolizing response associated with loss of cellular fitness as a previously underappreciated vulnerability of NF1-deficient cells and provide a disease-relevant framework for understanding curcumin responsiveness in NF1.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Molecular Biology and Pathology, National Research Council, 00185 Rome, Italy"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Assunta Maria Iazzetta",
      "orcid": "0009-0007-1439-1603"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesca Sardina",
      "orcid": "0000-0001-6474-2079"
    },
    {
      "affs": [
        0
      ],
      "name": "Cinzia Rinaldo",
      "orcid": "0000-0001-6124-762X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4xegpw06mck32.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15201904",
  "fulltext_url": "https://europepmc.org/articles/PMC13703259",
  "id": "4xegpw06mck32",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://www.mdpi.com/2073-4409/15/20/1904",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2728|Neurofibromatosis and Schwannoma Cases"
    ]
  ],
  "openalex": "W7223004227",
  "pdf_url": "https://europepmc.org/articles/PMC13703259?pdf=render",
  "pmcid": "PMC13703259",
  "pmid": "42929876",
  "published": "2026-10-20",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/4xegpw06mck32.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:02Z",
      "native_id": "10.3390/cells15201904",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/20/1904"
    },
    {
      "first_seen": "2026-10-30T12:22:01Z",
      "native_id": "MED:42929876",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42929876"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Neurofibromatosis and Schwannoma Cases",
      "subfield": "neurology"
    }
  ],
  "title": "Curcumin-Induced Vacuolizing Stress Reveals a Vulnerability Associated with NF1 Loss in Schwann Cells",
  "title_text": "Curcumin-Induced Vacuolizing Stress Reveals a Vulnerability Associated with NF1 Loss in Schwann Cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:01Z",
  "url": "https://research.draconitic.com/paper/4xegpw06mck32",
  "venue": "Cells",
  "versions": []
}