The balance between cathepsin C and cystatin F controls remyelination in the brain of Plp1-overexpressing mouse, a chronic demyelinating disease model

Takahiro Shimizu, Wilaiwan Wisessmith, Jiayi Li, Manabu Abe, Kenji Sakimura, Banthit Chetsawang, Yoshinori Sahara, Koujiro Tohyama, Kenji Tanaka, Kazuhiro Ikenaka

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

In demyelinating diseases such as multiple sclerosis (MS), an imbalance between the demyelination and remyelination rates underlies the degenerative processes. Microglial activation is observed in demyelinating lesions; however, the molecular mechanism responsible for the homeostatic/environmental change remains elusive. We previously found that cystatin F (CysF), a cysteine protease inhibitor, is selectively expressed in microglia only in actively demyelinating/remyelinating lesions but ceases expression in chronic lesions, suggesting its role in remyelination. Here, we report the effects of manipulating the expression of CysF and cathepsin C (CatC), a key target of CysF, in a murine model of transgenic demyelinating disease, Plp4e/-. During the active remyelinating phase, both CysF knockdown (CysFKD) and microglial-selective CatC overexpression (CatCOE) showed a worsening of the demyelination in Plp4e/- transgenic mice. Conversely, during the chronic demyelinating phase, CatC knockdown (CatCKD) ameliorated the demyelination. Our results suggest that the balance between CatC and CysF expression controls the demyelination and remyelination process.

Original languageEnglish
JournalGLIA
DOIs
Publication statusAccepted/In press - 2017

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Cathepsin C
Cystatins
Demyelinating Diseases
Chronic Disease
Brain
Cysteine Proteinase Inhibitors
Cystatin C
Microglia
Transgenic Mice
Multiple Sclerosis

Keywords

  • Cysteine protease inhibitor
  • Demyelination
  • Microglia
  • Remyelination

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

The balance between cathepsin C and cystatin F controls remyelination in the brain of Plp1-overexpressing mouse, a chronic demyelinating disease model. / Shimizu, Takahiro; Wisessmith, Wilaiwan; Li, Jiayi; Abe, Manabu; Sakimura, Kenji; Chetsawang, Banthit; Sahara, Yoshinori; Tohyama, Koujiro; Tanaka, Kenji; Ikenaka, Kazuhiro.

In: GLIA, 2017.

Research output: Contribution to journalArticle

Shimizu, Takahiro ; Wisessmith, Wilaiwan ; Li, Jiayi ; Abe, Manabu ; Sakimura, Kenji ; Chetsawang, Banthit ; Sahara, Yoshinori ; Tohyama, Koujiro ; Tanaka, Kenji ; Ikenaka, Kazuhiro. / The balance between cathepsin C and cystatin F controls remyelination in the brain of Plp1-overexpressing mouse, a chronic demyelinating disease model. In: GLIA. 2017.
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