Abstract
While proteolytic enzymes are involved in the pathogenesis of multiple sclerosis (MS), the involvement of cathepsins has not been characterized in detail. To better understand the role of cathepsins, cDNA microarray analysis was used to study the brains of proteolipid protein transgenic (plptg /-) mice, an animal model that closely mimics the failure of remyelination in MS. Analysis revealed upregulated expression of cathepsins L, H and B and their inhibitor, cystatin C. By in situ hybridization, the induction of cathepsins was primarily limited to microglia/macrophages of the white matter, with continuous expression from 2 to 8 months of age. Elevated protein level of cathepsins was confirmed at 4 months of age. In contrast, elevated expression of cystatin C was found in astrocytes. The ratio of microglia/macrophages to astrocytes increased throughout the course of demyelination, suggesting that the ratio of secreted cathepsins to cystatin C increased during that period. We propose that in MS, remyelination may be impaired by increasing activity of cathepsins inadequately controlled by cystatin C.
| Original language | English |
|---|---|
| Pages (from-to) | 311-320 |
| Number of pages | 10 |
| Journal | Neurochemical Research |
| Volume | 32 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2007 Feb |
| Externally published | Yes |
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Keywords
- Brain
- Cathepsin
- Cystatin C
- Demyelination
- In situ hybridization
ASJC Scopus subject areas
- Biochemistry
- Neuroscience(all)
Cite this
Induced expression of cathepsins and cystatin C in a murine model of demyelination. / Ma, Jianmei; Tanaka, Kenji; Yamada, Gen; Ikenaka, Kazuhiro.
In: Neurochemical Research, Vol. 32, No. 2, 02.2007, p. 311-320.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induced expression of cathepsins and cystatin C in a murine model of demyelination
AU - Ma, Jianmei
AU - Tanaka, Kenji
AU - Yamada, Gen
AU - Ikenaka, Kazuhiro
PY - 2007/2
Y1 - 2007/2
N2 - While proteolytic enzymes are involved in the pathogenesis of multiple sclerosis (MS), the involvement of cathepsins has not been characterized in detail. To better understand the role of cathepsins, cDNA microarray analysis was used to study the brains of proteolipid protein transgenic (plptg /-) mice, an animal model that closely mimics the failure of remyelination in MS. Analysis revealed upregulated expression of cathepsins L, H and B and their inhibitor, cystatin C. By in situ hybridization, the induction of cathepsins was primarily limited to microglia/macrophages of the white matter, with continuous expression from 2 to 8 months of age. Elevated protein level of cathepsins was confirmed at 4 months of age. In contrast, elevated expression of cystatin C was found in astrocytes. The ratio of microglia/macrophages to astrocytes increased throughout the course of demyelination, suggesting that the ratio of secreted cathepsins to cystatin C increased during that period. We propose that in MS, remyelination may be impaired by increasing activity of cathepsins inadequately controlled by cystatin C.
AB - While proteolytic enzymes are involved in the pathogenesis of multiple sclerosis (MS), the involvement of cathepsins has not been characterized in detail. To better understand the role of cathepsins, cDNA microarray analysis was used to study the brains of proteolipid protein transgenic (plptg /-) mice, an animal model that closely mimics the failure of remyelination in MS. Analysis revealed upregulated expression of cathepsins L, H and B and their inhibitor, cystatin C. By in situ hybridization, the induction of cathepsins was primarily limited to microglia/macrophages of the white matter, with continuous expression from 2 to 8 months of age. Elevated protein level of cathepsins was confirmed at 4 months of age. In contrast, elevated expression of cystatin C was found in astrocytes. The ratio of microglia/macrophages to astrocytes increased throughout the course of demyelination, suggesting that the ratio of secreted cathepsins to cystatin C increased during that period. We propose that in MS, remyelination may be impaired by increasing activity of cathepsins inadequately controlled by cystatin C.
KW - Brain
KW - Cathepsin
KW - Cystatin C
KW - Demyelination
KW - In situ hybridization
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U2 - 10.1007/s11064-006-9183-y
DO - 10.1007/s11064-006-9183-y
M3 - Article
VL - 32
SP - 311
EP - 320
JO - Neurochemical Research
JF - Neurochemical Research
SN - 0364-3190
IS - 2
ER -