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 language | English |
|---|---|
| Journal | GLIA |
| DOIs | |
| Publication status | Accepted/In press - 2017 |
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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 journal › Article
}
TY - JOUR
T1 - The balance between cathepsin C and cystatin F controls remyelination in the brain of Plp1-overexpressing mouse, a chronic demyelinating disease model
AU - Shimizu, Takahiro
AU - Wisessmith, Wilaiwan
AU - Li, Jiayi
AU - Abe, Manabu
AU - Sakimura, Kenji
AU - Chetsawang, Banthit
AU - Sahara, Yoshinori
AU - Tohyama, Koujiro
AU - Tanaka, Kenji
AU - Ikenaka, Kazuhiro
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Cysteine protease inhibitor
KW - Demyelination
KW - Microglia
KW - Remyelination
UR - http://www.scopus.com/inward/record.url?scp=85014119439&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014119439&partnerID=8YFLogxK
U2 - 10.1002/glia.23134
DO - 10.1002/glia.23134
M3 - Article
JO - GLIA
JF - GLIA
SN - 0894-1491
ER -