Extracellular neurosin degrades α-synuclein in cultured cells

被引：63

作者：

Tatebe, Harutsugu ^{[2
]}

Watanabe, Yoshihisa ^{[1
]}

Kasai, Takashi ^{[2
]}

Mizuno, Toshiki ^{[2
]}

Nakagawa, Masanori ^{[2
]}

Tanaka, Masaki ^{[1
]}

Tokuda, Takahiko ^{[2
]}

机构：

[1] Kyoto Prefectural Univ Med, Dept Cell Biol, Res Inst Neurol Dis & Geriatr, Kamikyo Ku, Kyoto 6020841, Japan

[2] Kyoto Prefectural Univ Med, Dept Neurol, Res Inst Neurol Dis & Geriatr, Kyoto 6020841, Japan

来源：

NEUROSCIENCE RESEARCH | 2010年 / 67卷 / 04期

关键词：

Neurosin; KLK6; alpha-Synuclein; Extracellular; Proteolytic activity; Cell line; SERINE-PROTEASE NEUROSIN; HUMAN KALLIKREIN 6; PARKINSONS-DISEASE; ZYME/PROTEASE M/NEUROSIN; CLINICAL-APPLICATIONS; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; MOLECULAR-CLONING; BRAIN; EXPRESSION;

D O I：

10.1016/j.neures.2010.04.008

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Neurosin, also called kallikrein 6, is a trypsin-like senile protease predominantly expressed in the central nervous system. Neurosis may degrade alpha-synuclein, a major component of the Lewy bodies commonly observed in dopaminergic neurons of patients with sporadic Parkinson's disease. In the present study, we investigated the localization and proteolytic activity of human neurosin using cultured cells to elucidate the physiological role of this enzyme at the cellular level. Heterologous expression of pre-pro-neurosin was localized to the endoplasmic reticulum and secreted. The proteolytic activity of neurosin was analyzed by zymography and fluorescent substrate, and showed that extracellular neurosis had protease activity but intracellular neurosin did not. We also coexpressed alpha-synuclein with neurosin and demonstrated that alpha-synuclein was not cleaved within cells, but extracellular alpha-synuclein was degraded by secreted neurosin. These findings suggest that neurosis targets the extracellular alpha-synuclein. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

引用

页码：341 / 346

页数：6

共 27 条

[1] A novel protease homolog differentially expressed in breast and ovarian cancer [J].