The Open Neurology Journal

ISSN: 1874-205X ― Volume 14, 2020

Enhanced Phosphorylation of Bax and Its Translocation into Mitochondria in the Brains of Individuals Affiliated with Alzheimer’s Disease

L.E. Henderson1, M.A. Abdelmegeed1, S.H. Yoo1, S.G. Rhee2, X. Zhu3, M.A. Smith3, R.Q. Nguyen4, G. Perry4, *, B.J. Song1, *
1 Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-9410, USA
2 Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
3 Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
4 Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA



Despite increased neuronal death, senile plaques, and neurofibrillary tangles observed in patients suffering from Alzheimer’s disease (AD), the detailed mechanism of cell death in AD is still poorly understood.


We hypothesized that p38 kinase activates and then phosphorylates Bax, leading to its translocation to mitochondria in AD brains compared to controls. The aim of this study was to investigate the role of p38 kinase in phosphorylation and sub-cellular localization of pro-apoptotic Bax in the frontal cortex of the brains from AD and control subjects. Increased oxidative stress in AD individuals compared to control was evaluated by measuring the levels of carbonylated proteins and oxidized peroxiredoxin, an antioxidant enzyme. The relative amounts of p38 kinase and phospho-Bax in mitochondria in AD brains and controls were determined by immunoblot analysis using the respective antibody against each protein following immunoprecipitation.


Our results showed that the levels of oxidized peroxiredoxin-SO3 and carbonylated proteins are significantly elevated in AD brains compared to controls, demonstrating the increased oxidative stress.


The amount of phospho-p38 kinase is increased in AD brains and the activated p38 kinase appears to phosphorylate Thr residue(s) of Bax, which leads to its mitochondrial translocation, contributing to apoptosis and ultimately, neurodegeneration.

Keywords: Alzheimer’s disease, p38 kinase, Bax phosphorylation, Mitochondrial translocation, Apoptosis, Neurodegeneration.

Article Information

Identifiers and Pagination:

Year: 2017
Volume: 11
First Page: 48
Last Page: 58
Publisher Id: TONEUJ-11-48
DOI: 10.2174/1874205X01711010048

Article History:

Received Date: 11/07/2017
Revision Received Date: 05/09/2017
Acceptance Date: 10/10/2017
Electronic publication date: 16/11/2017
Collection year: 2017

© 2017 Henderson et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-9410, USA; Tel: +1-82-2-2740-8360; Fax: +1-301-594-3113; E-mail:; Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA; Tel: +12104584450; Fax: +12104584445; E-mail:

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