Title

Possible role of amyloid-beta, adenine nucleotide translocase and cyclophilin-D interaction in mitochondrial dysfunction of Alzheimer's disease

Authors

Prabhakar Singh¹, Shubhankar Suman², Sudhir Chandna² and Taposh Kumar Das¹*

Affiliation

¹Department of Anatomy, All India Institute of Medical Sciences, New Delhi-110029, India; ²Natural Radiation Response Mechanisms Group, Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Delhi-110054, India;

Email

tkdas@aiims.ac.in

Article Type

Hypothesis

Date

Received April 06, 2009; accepted May 22, 2009; published August 04, 2009

Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by both extra- as well as intracellular deposition of amyloid beta peptides (Aβ). The accumulation of Aβ in mitochondria is associated with mitochondrial dysfunction and oxidative stress in AD. Recent evidences suggest the involvement of Aβ interaction with mitochondrial proteins such as cyclophilin-D (CypD) in oxidative stress, mitochondrial permeability transition (MPT) and Alzheimer’s associated neurodegeneration. The present study is an effort to elucidate the molecular interaction of Aβ with other proteins involved in MPT like adenine nucleotide translocase (ANT). Based on our prediction for sub-cellular localization using WolfPSORT and other experimental evidences, we suggest that Aβ molecules localize in mitochondrial inner membrane in close vicinity with ANT. Our simulation study for protein–protein interaction clearly suggests that the ANT-Aβ interaction is stronger than CypD-Aβ interaction. Further the lipophilic nature and evidences regarding the localization of Aβ in the mitochondrial inner-membrane also support the possibility of strong interaction between ANT and Aβ. Interaction between ANT and Aβ may affect normal physiological function of ANT i.e. transport of ATP and ADP. Since both the CypD-Aβ as well as ANT-Aβ interaction are energetically favorable and both CypD and ANT are associated with the regulation of MPT, the functional impact of both these interactions warrants more in-depth investigations for elucidating the mechanisms involved in Aβ-induced oxidative stress.

Keywords

Alzheimer; amyloid beta peptide; adenine nucleotide translocase; voltage dependent anion channel; mitochondrial permeability

Citation

Singh et al., Bioinformation 3(10): 440-445 (2009)

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.