Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Zhang, Jia-yu | Peng, Caixia | Shi, Hairong | Wang, Shaohui | Wang, Qun | Wang, Jian-zhi; *
Affiliations: Department of Pathophysiology, Hubei Provincial Key Laboratory of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
Correspondence: [*] Corresponding author: Dr. Wang Jian-zhi, Department of Pathophysiology, Institute of Neuroscience, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P.R. China. Tel.: +86 27 83692625; Fax: +86 27 83693883; E-mail: wangjz@mails.tjmu.edu.cn.
Note: [] Communicated by Chengxin Gong
Abstract: The autophagic lysosomal system contributes to the removal of cytosolic components, and abnormality of lysosomal proteases has been reported in the brain of patients with Alzheimer's disease (AD). However, the role of lysosome in tau degradation is still elusive. Here, we infused chloroquine, 3-methyladenine or rapamycin into rat hippocampus or the lateral ventricle to manipulate the autophagic activity and measured the levels of tau protein by Western blotting. We unexpectedly observed that the level of different tau species decreased upon inhibition of lysosomal proteases or macroautophagy by chloroquine or 3-methyladenine. Furthermore, induction of autophagic activity by rapamycin did not induce degradation of tau proteins. To explore the underlying mechanisms for the increased tau degradation induced by autophagic inhibition, we used MG-132, an inhibitor of proteasome and calpain. We found that simultaneous inhibition of proteasome and calpain by MG-132 prevented the chloroquine-induced tau degradation. Further studies demonstrated that the activity of calpain was elevated whereas the activity of proteasome was suppressed in response to inhibition of autophagy by 3-methyladenine or chloroquine. Our data suggest that the lysosomal autophagic system may not degrade tau in the normal adult rat brain and inhibition of autophagy may induce tau proteolysis through activating calpain.
Keywords: Autophagy, calpain, degradation, tau
DOI: 10.3233/JAD-2009-0908
Journal: Journal of Alzheimer's Disease, vol. 16, no. 1, pp. 39-47, 2009
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
sales@iospress.com
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
info@iospress.nl
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office info@iospress.nl
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
china@iospress.cn
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
如果您在出版方面需要帮助或有任何建, 件至: editorial@iospress.nl