Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum

Yuichi Abe, Masanori Honsho, Ryota Itoh, Ryoko Kawaguchi, Masashi Fujitani, Kazushirou Fujiwara, Masaaki Hirokane, Takashi Matsuzaki, Keiko Nakayama, Ryohei Ohgi, Toshihiro Marutani, Keiichi I. Nakayama, Toshihide Yamashita, Yukio Fujiki

研究成果: ジャーナルへの寄稿学術誌査読

14 被引用数 (Scopus)


Peroxisome biogenesis disorders (PBDs) manifest as neurological deficits in the central nervous system, including neuronal migration defects and abnormal cerebellum development. However, the mechanisms underlying pathogenesis remain enigmatic. Here, to investigate how peroxisome deficiency causes neurological defects of PBDs, we established a new PBD model mouse defective in peroxisome assembly factor Pex14p, termed Pex14ΔC/ΔC mouse. Pex14ΔC/ΔC mouse manifests a severe symptom such as disorganization of cortical laminar structure and dies shortly after birth, although peroxisomal biogenesis and metabolism are partially defective. The Pex14ΔC/ΔC mouse also shows malformation of the cerebellum including the impaired dendritic development of Purkinje cells. Moreover, extracellular signal-regulated kinase and AKT signaling are attenuated in this mutant mouse by an elevated level of brain-derived neurotrophic factor (BDNF) together with the enhanced expression of TrkB-T1, a dominant-negative isoform of the BDNF receptor. Our results suggest that dysregulation of the BDNF-TrkB pathway, an essential signaling for cerebellar morphogenesis, gives rise to the pathogenesis of the cerebellum in PBDs.

ジャーナルLife Science Alliance
出版ステータス出版済み - 2018

!!!All Science Journal Classification (ASJC) codes

  • 生態学
  • 生化学、遺伝学、分子生物学(その他)
  • 植物科学
  • 健康、毒物学および変異誘発


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