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Peer-reviewedCC BY 4.0PLOS One

Chromogranin B acts as a neuronal paracrine factor to trigger oligodendrocyte apoptosis

  1. 1Department of Clinical Bioanalysis and Molecular Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo/Tokyo Medical and Dental University (TMDU), Tokyo, Japan
  2. 2Department of Molecular and Cellular Biology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo/TMDU, Tokyo, Japan

Abstract

Various soluble factors, such as inflammatory cytokines and autoantibodies secreted by activated microglia, macrophages, and astrocytes, are known to promote death of oligodendrocyte (OL) lineage cells, including OLs and OL precursor cells (OPCs), in the central nervous system during demyelination of multiple sclerosis. However, the role of factors secreted by neurons in OL lineage cell death remains underexplored. Chromogranin B (Chgb), a critical protein for secretory granule formation in neuroendocrine cells, is also specifically expressed and secreted from neurons. In this study, we investigated the effect of extracellular Chgb on OL lineage cells. We found that treatment with recombinant mouse or human Chgb significantly reduced the population of both mature OLs and OPCs by inducing apoptosis. This Chgb-induced apoptosis was effectively suppressed by an anti-Chgb antibody. Furthermore, in neuron-OPC/OL cocultures, endogenous Chgb secreted by neurons similarly promoted OL apoptosis, an effect that was also neutralized by the anti-Chgb antibody. Collectively, these results identify Chgb as a neuronal paracrine factor that triggers apoptotic death in OL lineage cells. Our findings provide new insights into the regulation of OL lineage cell death by neuronal secretion factors.

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BibTeX
@article{yamada2026chromogranin,
  title = {{Chromogranin B acts as a neuronal paracrine factor to trigger oligodendrocyte apoptosis}},
  author = {Nanako Yamada and Momona Yamada and Reina Ono and Binri Sasaki and Sakurako Abe and Tomoka Aoki and Akira Yoshimoto and Ryunosuke Ohkawa and Nobuharu Suzuki},
  journal = {PLOS One},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pone.0358362},
  url = {https://doi.org/10.1371/journal.pone.0358362},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Chromogranin B acts as a neuronal paracrine factor to trigger oligodendrocyte apoptosis
AU  - Nanako Yamada
AU  - Momona Yamada
AU  - Reina Ono
AU  - Binri Sasaki
AU  - Sakurako Abe
AU  - Tomoka Aoki
AU  - Akira Yoshimoto
AU  - Ryunosuke Ohkawa
AU  - Nobuharu Suzuki
PY  - 2026
DA  - 2026/09/21
JO  - PLOS One
DO  - 10.1371/journal.pone.0358362
UR  - https://doi.org/10.1371/journal.pone.0358362
AB  - Various soluble factors, such as inflammatory cytokines and autoantibodies secreted by activated microglia, macrophages, and astrocytes, are known to promote death of oligodendrocyte (OL) lineage cells, including OLs and OL precursor cells (OPCs), in the central nervous system during demyelination of multiple sclerosis. However, the role of factors secreted by neurons in OL lineage cell death remains underexplored. Chromogranin B (Chgb), a critical protein for secretory granule formation in neuroendocrine cells, is also specifically expressed and secreted from neurons. In this study, we investigated the effect of extracellular Chgb on OL lineage cells. We found that treatment with recombinant mouse or human Chgb significantly reduced the population of both mature OLs and OPCs by inducing apoptosis. This Chgb-induced apoptosis was effectively suppressed by an anti-Chgb antibody. Furthermore, in neuron-OPC/OL cocultures, endogenous Chgb secreted by neurons similarly promoted OL apoptosis, an effect that was also neutralized by the anti-Chgb antibody. Collectively, these results identify Chgb as a neuronal paracrine factor that triggers apoptotic death in OL lineage cells. Our findings provide new insights into the regulation of OL lineage cell death by neuronal secretion factors.
SN  - 1932-6203
ER  -