Alpha 1-Antichymotrypsin, an Inflammatory Protein Overexpressed in the Brains of Patients with Alzheimer’s Disease, Induces Tau Hyperphosphorylation through c-Jun N-Terminal Kinase Activation
Joint Authors
Padmanabhan, Jaya
Tyagi, Ethika
Norden, Michelle
Fiorelli, Tina
Source
International Journal of Alzheimer's Disease
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-09-23
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
The association of inflammatory proteins with neuritic plaques in the brains of Alzheimer’s disease (AD) patients has led to the hypothesis that inflammation plays a pivotal role in the development of pathology in AD.
Earlier studies have shown that alpha 1-antichymotrypsin (ACT) enhances amyloid beta fibrillization and accelerated plaque formation in APP transgenic mice.
Later studies from our laboratory have shown that purified ACT induces tau hyperphosphorylation and degeneration in neurons.
In order to understand the mechanisms by which inflammatory proteins enhance tau hyperphosphorylation, we injected interleukin-1β (IL-1β) intracerebroventricularly into mice expressing human ACT, human tau, or both transgenes.
It was found that the hyperphosphorylation of tau in ACT and ACT/htau mice after IL-1β injection correlated with increased phosphorylation of c-Jun N-terminal kinase (JNK).
We verified the involvement of JNK in ACT-induced tau phosphorylation by utilizing JNK inhibitors in cultured primary neurons treated with ACT, and we found that the inhibitor showed complete prevention of ACT-induced tau phosphorylation.
These results indicate that JNK is one of the major kinases involved in the ACT-mediated tau hyperphosphorylation and suggest that inhibitors of this kinase may protect against inflammation-induced tau hyperphosphorylation and neurodegeneration associated with AD.
American Psychological Association (APA)
Tyagi, Ethika& Fiorelli, Tina& Norden, Michelle& Padmanabhan, Jaya. 2013. Alpha 1-Antichymotrypsin, an Inflammatory Protein Overexpressed in the Brains of Patients with Alzheimer’s Disease, Induces Tau Hyperphosphorylation through c-Jun N-Terminal Kinase Activation. International Journal of Alzheimer's Disease،Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-1005914
Modern Language Association (MLA)
Tyagi, Ethika…[et al.]. Alpha 1-Antichymotrypsin, an Inflammatory Protein Overexpressed in the Brains of Patients with Alzheimer’s Disease, Induces Tau Hyperphosphorylation through c-Jun N-Terminal Kinase Activation. International Journal of Alzheimer's Disease No. 2013 (2013), pp.1-11.
https://search.emarefa.net/detail/BIM-1005914
American Medical Association (AMA)
Tyagi, Ethika& Fiorelli, Tina& Norden, Michelle& Padmanabhan, Jaya. Alpha 1-Antichymotrypsin, an Inflammatory Protein Overexpressed in the Brains of Patients with Alzheimer’s Disease, Induces Tau Hyperphosphorylation through c-Jun N-Terminal Kinase Activation. International Journal of Alzheimer's Disease. 2013. Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-1005914
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1005914