Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 130, Issue 9, Pages 592-601Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2009.07.002
Keywords
Alzheimer's disease; Amyloid precursor protein; Heat-shock proteins; Bcl-2; Mitochondria; Apoptosis
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Funding
- China Medical University, Taichung, Taiwan [CMU97-111, CMU96-235, CMU95-314]
- Ministry of Education, Taiwan
- NCKU Project of Promoting Academic Excellence & Developing World Class Research Centers
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Neurons that degenerate in the brains of persons with Alzheimer's disease accumulate mitochondrial amyloid precursor protein (APP), which is thought to negatively affect mitochondrial function and cellular homeostasis. Because proteins that enter mitochondria require assistance from chaperone proteins, we hypothesized that heat-shock proteins (HSPs) help accumulate APP in mitochondria. We found that APP overexpression in N2a cells (APP cells) did not elicit mitochondrial dysfunction. Because cerebral hypoperfusion-associated energy deficiency is an important etiology for Alzheimer's disease, we also challenged the cells with serum starvation. APP/HSP/Bcl-2 complexes formed within the mitochondria of serum-starved APP cells, but not control cells. Mitochondria containing APP/HSP/Bcl-2 complexes induced apoptosis. We hypothesize that APP/HSP/Bcl-2 complexes diminish the functional capacities of HSPs and Bcl-2, which leads to mitochondrial injury and apoptosis. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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