Abstract
Recently, attention has been paid to intracellular proteinase functions in relation to the process of neuronal cell death, and defining how they are involved is essential for developing neuro protective strategies as well as for understanding the pathology of neurodegerative diseases. Several recent articles have outlined the activation and deleterious effect of μ-calpain, a calcium activated cysteine proteinase, on the cytoskeleton protein network, which is thought to lead to cell death. Furthermore, a marked increase in cathepsins B, L, and D, lysosomal proteinases, and cathepsin E, non-lysosomal aspartic proteinase, in neurons has been shown in the early stage of neuronal degeneration. The increased levels of these lysosomal cathepsins in degenerating neurons are considered to be associated with stimulated autophagy, which occasionally can lead to neuronal cell death. The molecular form of cathepsin E accumulated in affected neurons was different from that of the normal cathepsin E molecule. This unusual molecular form of cathepsin E is likely to be critical for disruption of normal cellular function, possibly culminating in neuronal cell death. The increased level of such proteinases was also found in reactive glial cells. In these cells, cathepsin E was increased as a mature form exclusively in reactive microglial cells, while cathepsins D and G were increased mainly in reactive astrocytes. Overproduction of cathepsins E, D and G in these reactive glial cells may be finally involved in the pathogenesis of neuro degenerative disease.
| Original language | English |
|---|---|
| Pages (from-to) | 1-9 |
| Number of pages | 9 |
| Journal | Folia Pharmacologica Japonica |
| Volume | 105 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 1995 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
Cite this
Neuronal cell death and intracellular proteinase functions. / Nakanishi, Hiroshi; Yamamoto, Kenji.
In: Folia Pharmacologica Japonica, Vol. 105, No. 1, 01.01.1995, p. 1-9.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neuronal cell death and intracellular proteinase functions
AU - Nakanishi, Hiroshi
AU - Yamamoto, Kenji
PY - 1995/1/1
Y1 - 1995/1/1
N2 - Recently, attention has been paid to intracellular proteinase functions in relation to the process of neuronal cell death, and defining how they are involved is essential for developing neuro protective strategies as well as for understanding the pathology of neurodegerative diseases. Several recent articles have outlined the activation and deleterious effect of μ-calpain, a calcium activated cysteine proteinase, on the cytoskeleton protein network, which is thought to lead to cell death. Furthermore, a marked increase in cathepsins B, L, and D, lysosomal proteinases, and cathepsin E, non-lysosomal aspartic proteinase, in neurons has been shown in the early stage of neuronal degeneration. The increased levels of these lysosomal cathepsins in degenerating neurons are considered to be associated with stimulated autophagy, which occasionally can lead to neuronal cell death. The molecular form of cathepsin E accumulated in affected neurons was different from that of the normal cathepsin E molecule. This unusual molecular form of cathepsin E is likely to be critical for disruption of normal cellular function, possibly culminating in neuronal cell death. The increased level of such proteinases was also found in reactive glial cells. In these cells, cathepsin E was increased as a mature form exclusively in reactive microglial cells, while cathepsins D and G were increased mainly in reactive astrocytes. Overproduction of cathepsins E, D and G in these reactive glial cells may be finally involved in the pathogenesis of neuro degenerative disease.
AB - Recently, attention has been paid to intracellular proteinase functions in relation to the process of neuronal cell death, and defining how they are involved is essential for developing neuro protective strategies as well as for understanding the pathology of neurodegerative diseases. Several recent articles have outlined the activation and deleterious effect of μ-calpain, a calcium activated cysteine proteinase, on the cytoskeleton protein network, which is thought to lead to cell death. Furthermore, a marked increase in cathepsins B, L, and D, lysosomal proteinases, and cathepsin E, non-lysosomal aspartic proteinase, in neurons has been shown in the early stage of neuronal degeneration. The increased levels of these lysosomal cathepsins in degenerating neurons are considered to be associated with stimulated autophagy, which occasionally can lead to neuronal cell death. The molecular form of cathepsin E accumulated in affected neurons was different from that of the normal cathepsin E molecule. This unusual molecular form of cathepsin E is likely to be critical for disruption of normal cellular function, possibly culminating in neuronal cell death. The increased level of such proteinases was also found in reactive glial cells. In these cells, cathepsin E was increased as a mature form exclusively in reactive microglial cells, while cathepsins D and G were increased mainly in reactive astrocytes. Overproduction of cathepsins E, D and G in these reactive glial cells may be finally involved in the pathogenesis of neuro degenerative disease.
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U2 - 10.1254/fpj.105.1
DO - 10.1254/fpj.105.1
M3 - Article
C2 - 7721188
AN - SCOPUS:0028821675
VL - 105
SP - 1
EP - 9
JO - Folia Pharmacologica Japonica
JF - Folia Pharmacologica Japonica
SN - 0015-5691
IS - 1
ER -