Targeting Mitochondrial Redox Signaling Promotes Neuroregeneration and Functional Recovery in a Multiple Sclerosis Model.
10 affiliations
- 1Faculty of Science and Technology, Keio University, Yokohama-shi, Kanagawa, Japan.
- 2Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
- 3Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
- 4Graduate School of Pharmaceutical Sciences, Chiba University, Chiba-shi, Chiba, Japan.
- 5Department of Pathology, Faculty of Veterinary Medicine, Beni-Suef University (BSU), Beni-Suef, Egypt.
- 6RIKEN CSRS, Wako-shi, Saitama, Japan.
- 7Institute of Microbial Chemistry (BIKAKEN), Shinagawa-ku, Tokyo, Japan.
- 8Department of Computer Science, School of Computing, Institute of Science Tokyo, Yokohama-shi, Kanagawa, Japan.
- 9Graduate School of Science, Chiba University, Chiba-shi, Chiba, Japan.
- 10Beckman Institute for Advanced Science and Technology, Urbana, Illinois, USA.
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.
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BibTeX
@article{narushima2026targeting,
title = {{Targeting Mitochondrial Redox Signaling Promotes Neuroregeneration and Functional Recovery in a Multiple Sclerosis Model.}},
author = {Yuki Narushima and Joshua Saylor and Shun Saito and Jinyan Zhou and Haruka Kawano and Shehata Anwar and Haruki Oba and Rachel Huezo and Miyu Okano and Haruki Matsuda and Makoto Kawatani and Kaori Honda and Hiroyuki Osada and Yuta Kikuchi and Masahito Ohue and Masami Ishibashi and Takayoshi Arai and Makoto Inoue and Midori A Arai},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78560},
url = {https://europepmc.org/article/MED/42960836},
note = {CC BY},
}
RIS
TY - JOUR
TI - Targeting Mitochondrial Redox Signaling Promotes Neuroregeneration and Functional Recovery in a Multiple Sclerosis Model.
AU - Yuki Narushima
AU - Joshua Saylor
AU - Shun Saito
AU - Jinyan Zhou
AU - Haruka Kawano
AU - Shehata Anwar
AU - Haruki Oba
AU - Rachel Huezo
AU - Miyu Okano
AU - Haruki Matsuda
AU - Makoto Kawatani
AU - Kaori Honda
AU - Hiroyuki Osada
AU - Yuta Kikuchi
AU - Masahito Ohue
AU - Masami Ishibashi
AU - Takayoshi Arai
AU - Makoto Inoue
AU - Midori A Arai
PY - 2026
DA - 2026/10/30
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78560
UR - https://europepmc.org/article/MED/42960836
AB - 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.
SN - 2198-3844
ER -