Computational Studies of Beta Amyloid Aβ42 with p75NTR Receptor: A Novel Therapeutic Target in Alzheimer’s DiseaseReportar como inadecuado

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Advances in Bioinformatics - Volume 2014 2014, Article ID 736378, 6 pages -

Research Article

Department of Biotechnology and Bioinformatics, Dr. D. Y. Patil University, Navi Mumbai, Maharashtra 400614, India

Department of Nanoscience and Technology, Tamil Nadu Agricultural University, Coimbatore 641003, India

Received 2 June 2014; Accepted 18 October 2014; Published 11 November 2014

Academic Editor: Alexander Zelikovsky

Copyright © 2014 Shine Devarajan and Jeya Sundara Sharmila. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Alzheimer’s disease is a neurodegenerative disorder characterized by the accumulation of beta amyloid plaques Aβ which can induce neurite degeneration and progressive dementia. It has been identified that neuronal apoptosis is induced by binding of Aβ42 to pan neurotrophin receptor p75NTR and gave the possibility that beta amyloid oligomer is a ligand for p75NTR. However, the atomic contact point responsible for molecular interactions and conformational changes of the protein upon binding was not studied in detail. In view of this, we conducted a molecular docking and simulation study to investigate the binding behaviour of Aβ42 monomer with p75NTR ectodomain. Furthermore, we proposed a p75NTR-ectodomain-Aβ42 complex model. Our data revealed that, Aβ42 specifically recognizes CRD1 and CRD2 domains of the receptor and formed a “cap” like structure at the N-terminal of receptor which is stabilized by a network of hydrogen bonds. These findings are supported by molecular dynamics simulation that Aβ42 showed distinct structural alterations at N- and C-terminal regions due to the influence of the receptor binding site. Overall, the present study gives more structural insight on the molecular interactions of beta amyloid protein involved in the activation of p75NTR receptor.

Autor: Shine Devarajan and Jeya Sundara Sharmila



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