{
  "abstract": "Neurodegenerative diseases, including multiple sclerosis (MS), are characterized by progressive neuronal loss and limited regenerative capacity. To stimulate in vivo neurogenesis and oligodendrogenesis by harnessing the untapped regenerative potential of endogenous neural progenitor cells (NPCs) that are upregulated in the CNS under disease conditions, we developed a novel compound that targets Notch signaling, a pathway known to suppress neuronal differentiation of NPCs. Furapyrrodole, which was identified by screening a natural product-like synthetic chemical library, binds to and activates the mitochondrial reductase CYB5R3, which naturally downregulates Notch signaling downstream of γ-secretase. The in vivo efficacy of furapyrrodole was evaluated in mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Furapyrrodole treatment after the peak of EAE disease significantly improved motor function and promoted recovery of motor neurons and myelination by stimulating endogenous NPC-derived neurogenesis and oligodendrogenesis. In addition, furapyrrodole supresses neuroinflammation in the CNS. Collectively, these findings indicate furapyrrodole is a promising therapeutic candidate for MS by harnessing endogenously upregulated NPCs and inducing anti-inflammation. Our study demonstrates for the first time that modulation of mitochondrial redox signaling promotes neuroregeneration and remyelination without causing severe adverse effects.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Science and Technology, Keio University, Yokohama-shi, Kanagawa, Japan.",
    "Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.",
    "Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.",
    "Graduate School of Pharmaceutical Sciences, Chiba University, Chiba-shi, Chiba, Japan.",
    "Department of Pathology, Faculty of Veterinary Medicine, Beni-Suef University (BSU), Beni-Suef, Egypt.",
    "RIKEN CSRS, Wako-shi, Saitama, Japan.",
    "Institute of Microbial Chemistry (BIKAKEN), Shinagawa-ku, Tokyo, Japan.",
    "Department of Computer Science, School of Computing, Institute of Science Tokyo, Yokohama-shi, Kanagawa, Japan.",
    "Graduate School of Science, Chiba University, Chiba-shi, Chiba, Japan.",
    "Beckman Institute for Advanced Science and Technology, Urbana, Illinois, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yuki Narushima",
      "orcid": "0009-0009-3963-5971"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Joshua Saylor",
      "orcid": "0000-0002-3022-1387"
    },
    {
      "affs": [
        0
      ],
      "name": "Shun Saito",
      "orcid": "0000-0001-9270-4272"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Jinyan Zhou",
      "orcid": "0009-0004-6170-9440"
    },
    {
      "affs": [
        3
      ],
      "name": "Haruka Kawano"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Shehata Anwar"
    },
    {
      "affs": [
        0
      ],
      "name": "Haruki Oba"
    },
    {
      "affs": [
        1
      ],
      "name": "Rachel Huezo"
    },
    {
      "affs": [
        3
      ],
      "name": "Miyu Okano"
    },
    {
      "affs": [
        0
      ],
      "name": "Haruki Matsuda",
      "orcid": "0009-0004-7965-090X"
    },
    {
      "affs": [
        5
      ],
      "name": "Makoto Kawatani",
      "orcid": "0000-0002-9571-4916"
    },
    {
      "affs": [
        5
      ],
      "name": "Kaori Honda"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Hiroyuki Osada",
      "orcid": "0000-0002-3606-4925"
    },
    {
      "affs": [
        7
      ],
      "name": "Yuta Kikuchi"
    },
    {
      "affs": [
        7
      ],
      "name": "Masahito Ohue",
      "orcid": "0000-0002-0120-1643"
    },
    {
      "affs": [
        3
      ],
      "name": "Masami Ishibashi",
      "orcid": "0000-0002-2839-1045"
    },
    {
      "affs": [
        8
      ],
      "name": "Takayoshi Arai",
      "orcid": "0000-0001-9490-3988"
    },
    {
      "affs": [
        1,
        2,
        9
      ],
      "name": "Makoto Inoue",
      "orcid": "0000-0002-3991-3806"
    },
    {
      "affs": [
        0
      ],
      "name": "Midori A Arai",
      "orcid": "0000-0003-0254-9550"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dfh757a7q4667.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78560",
  "fulltext_url": "https://europepmc.org/articles/PMC13721028",
  "id": "dfh757a7q4667",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://europepmc.org/article/MED/42960836",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2806|Neurogenesis and neuroplasticity mechanisms"
    ]
  ],
  "openalex": "W7224935196",
  "pdf_url": "https://europepmc.org/articles/PMC13721028?pdf=render",
  "pmcid": "PMC13721028",
  "pmid": "42960836",
  "published": "2026-10-30",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/dfh757a7q4667.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:50Z",
      "native_id": "MED:42960836",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42960836"
    },
    {
      "first_seen": "2026-11-03T12:21:47Z",
      "native_id": "PMC13721028",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.78560"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2806|Neurogenesis and neuroplasticity mechanisms",
      "subfield": "neuroscience"
    }
  ],
  "title": "Targeting Mitochondrial Redox Signaling Promotes Neuroregeneration and Functional Recovery in a Multiple Sclerosis Model.",
  "title_text": "Targeting Mitochondrial Redox Signaling Promotes Neuroregeneration and Functional Recovery in a Multiple Sclerosis Model.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:47Z",
  "url": "https://research.draconitic.com/paper/dfh757a7q4667",
  "venue": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
  "versions": []
}