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Title

The role of CDK5 and GSK3B kinases in hyperphosphorylation of microtubule associated protein tau (MAPT) in Alzheimer’s disease

 

Authors

Saranya Jayapalan & Jeyakumar Natarajan*

 

Affiliation

1Department of Biotechnology and Bioinformatics, 2Department of Zoology, 3Departments of Genetics and Genomics, Yogi Vemana University, Kadapa, Andhra Pradesh, India-516 003

 

Email

n.jeyakumar@yahoo.co.in; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received October 10, 2013; Accepted December 04, 2013; Published December 27, 2013

 

Abstract

Alzheimer’s disease is the most common form of dementia. Abnormal hyperphosphorylation of Microtubule associated protein tau (MAPT) is one of the hallmarks of Alzheimer’s disease and related tau pathies. CDK5 and GSK3B are the two main protein kinases that have an important role in the abnormal hyperphosphorylation of MAPT which leads to Alzheimer’s disease. Structural information for both MAPT-CDK5 and MAPT-GSK3B complexes being absent, we resorted to molecular modeling for gaining insight into the mechanism of implication of hyperphosphorylation of MAPT by both enzymes. First the tertiary structure of MAPT was modeled and its active regions were defined. This was followed by molecular docking and interaction studies of MAPT with CDK5 and GSK3B kinases to infer the role of these kinases in abnormal hyperphosphorylation of MAPT protein. In addition, we have investigated the characteristic features such as phosphorylation sites and ATP binding sites of MAPT and two kinases. Further we computed the stabilization centers and stabilization residues of the MAPT protein and two kinases before and after docking process. The overall results portray that CDK5 is strongly involved in the hyperphosphorylation of MAPT when compared to GSK3B.

 

Keywords

Alzheimer’s, MAPT, CDK5, GSK3B, hyperphosphorylation.

 

Citation

Jayapalan & Natarajan,   Bioinformation 9(20): 1023-1030 (2013)

 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.