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The balance between cathepsin C and cystatin F controls remyelination in the brain of Plp1 ‐overexpressing mouse, a chronic demyelinating disease model
Author(s) -
Shimizu Takahiro,
Wisessmith Wilaiwan,
Li Jiayi,
Abe Manabu,
Sakimura Kenji,
Chetsawang Banthit,
Sahara Yoshinori,
Tohyama Koujiro,
Tanaka Kenji F.,
Ikenaka Kazuhiro
Publication year - 2017
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23134
Subject(s) - remyelination , demyelinating disease , genetically modified mouse , biology , multiple sclerosis , immunology , microglia , neuroscience , transgene , myelin , central nervous system , inflammation , genetics , gene
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, Plp 4e/‐ . During the active remyelinating phase, both CysF knockdown (CysFKD) and microglial‐selective CatC overexpression (CatCOE) showed a worsening of the demyelination in Plp 4e/‐ 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.