{
  "abstract": "The accumulation of α-synuclein (α-syn) in the form of Lewy bodies and Lewy neurites is a neuropathological hallmark of Parkinson’s disease (PD) and is closely associated with disease progression. Targeting the autophagy pathway to enhance the clearance of α-syn aggregates therefore represents a promising therapeutic strategy. In the present study, we conducted high-throughput screening using rat embryonic primary neurons, followed by validation of the identified compounds in human induced pluripotent stem cell (iPSC)-derived neurons. We identified dibucaine, a local anesthetic, as a compound that induced autophagic flux in neuronal models. In human iPSC-derived dopaminergic neurons from a patient with PD carrying an SNCA duplication, dibucaine reduced cellular levels of Ser129-phosphorylated α-synuclein (pS129 α-syn). In SH-SY5Y cells, dibucaine increased 5’-AMP-activated protein kinase (AMPK) Thr172 phosphorylation. LY364947 partially attenuated dibucaine-induced LC3-II accumulation in the iPSC-derived neurons through an unidentified mechanism. Although the requirement for AMPK and the mechanism underlying the reduction in pS129 α-syn remain unresolved, our findings show that dibucaine induces autophagic flux and reduces pS129 α-syn levels in disease-relevant human neurons.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, Juntendo University Faculty of Medicine",
    "Sumitomo Pharma Co., Ltd.",
    "Center for Genomic and Regenerative Medicine, Juntendo University Graduate School of Medicine",
    "Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine",
    "Division for Development of Autophagy Modulating Drugs, Juntendo University Faculty of Medicine",
    "Department of Neurology, Institute of Medicine, University of Tsukuba",
    "Neurodegenerative Disorders Collaboration Laboratory, RIKEN Center for Brain Science"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mitsuhiro Kitagawa"
    },
    {
      "affs": [
        1
      ],
      "name": "Kengo Miyamoto"
    },
    {
      "affs": [
        1
      ],
      "name": "Kozo Yoshida"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Kei-Ichi Ishikawa"
    },
    {
      "affs": [
        0,
        3,
        4
      ],
      "name": "Yukiko Sasazawa"
    },
    {
      "affs": [
        2
      ],
      "name": "Wado Akamatsu"
    },
    {
      "affs": [
        0,
        4,
        5
      ],
      "name": "Shinji Saiki"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Taku Hatano"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Masaya Imoto"
    },
    {
      "affs": [
        1
      ],
      "name": "Hidetaka Nagata"
    },
    {
      "affs": [
        0,
        3,
        5,
        6
      ],
      "name": "Nobutaka Hattori"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5kneww2rt6aq8.bib",
  "cited_by": 0,
  "doi": "10.3389/fneur.2026.1891393",
  "fulltext_url": "https://europepmc.org/articles/PMC13686833",
  "id": "5kneww2rt6aq8",
  "issns": [
    "1664-2295"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fneur.2026.1891393/full",
  "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|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7221041176",
  "pdf_url": "https://europepmc.org/articles/PMC13686833?pdf=render",
  "pmcid": "PMC13686833",
  "pmid": "42922803",
  "published": "2026-10-08",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/5kneww2rt6aq8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:16Z",
      "native_id": "10.3389/fneur.2026.1891393",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fneur.2026.1891393/full"
    },
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42922803",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42922803"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Dibucaine induces autophagic flux and reduces Ser129-phosphorylated α-synuclein in induced pluripotent stem cell–derived neurons with SNCA duplication",
  "title_text": "Dibucaine induces autophagic flux and reduces Ser129-phosphorylated α-synuclein in induced pluripotent stem cell–derived neurons with SNCA duplication",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/5kneww2rt6aq8",
  "venue": "Frontiers in Neurology",
  "versions": []
}