Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease
<p>Abstract</p> <p>Lewy bodies and Lewy neurites constitute the cardinal neuropathological features of both Parkinson's disease (PD) and Lewy body dementia (LBD). Whereas α-synuclein has been found to be the major component of the Lewy body, the mechanisms by which neurons deg...
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Series: | Molecular Neurodegeneration |
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doaj-92a27b0ae18a4909bed01ab98f7ac3442020-11-24T21:52:06ZengBMCMolecular Neurodegeneration1750-13262009-07-01413210.1186/1750-1326-4-32Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's diseasePerry GeorgeCastellani Rudy JTakeda AtsushiChoi RaymondKondo EisakuSiedlak Sandra LChen Shu GWang XinglongLiu HaihuaSu BoSmith Mark AZhu XiongweiLee Hyoung-gon<p>Abstract</p> <p>Lewy bodies and Lewy neurites constitute the cardinal neuropathological features of both Parkinson's disease (PD) and Lewy body dementia (LBD). Whereas α-synuclein has been found to be the major component of the Lewy body, the mechanisms by which neurons degenerate, as well as basic mechanisms involved in the formation of α-synuclein-related inclusions, remain obscure. We have suggested previously that potential mechanisms are likely to leave a "molecular signature" or protein adduct within the Lewy body, and have found examples of such signatures in previous studies. In this study, we demonstrate increased FOXO3 in association with Lewy bodies and Lewy neurites in LBD and PD brain tissue. Since FOXO proteins are involved in several pathways responsible for the regulation of cell death, cell proliferation, and cell metabolism, the ectopic localization of FOXO3 to Lewy bodies provides evidence that aberrations in basic cellular biochemistry may contribute to inclusion formation, which is likely more complex than a simple "gain of function" toxicity as is commonly opined. In light of the known interaction of FOXO3 and 14-3-3, basic protein-protein interaction between these proteins and α-synuclein may be key.</p> http://www.molecularneurodegeneration.com/content/4/1/32 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Perry George Castellani Rudy J Takeda Atsushi Choi Raymond Kondo Eisaku Siedlak Sandra L Chen Shu G Wang Xinglong Liu Haihua Su Bo Smith Mark A Zhu Xiongwei Lee Hyoung-gon |
spellingShingle |
Perry George Castellani Rudy J Takeda Atsushi Choi Raymond Kondo Eisaku Siedlak Sandra L Chen Shu G Wang Xinglong Liu Haihua Su Bo Smith Mark A Zhu Xiongwei Lee Hyoung-gon Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease Molecular Neurodegeneration |
author_facet |
Perry George Castellani Rudy J Takeda Atsushi Choi Raymond Kondo Eisaku Siedlak Sandra L Chen Shu G Wang Xinglong Liu Haihua Su Bo Smith Mark A Zhu Xiongwei Lee Hyoung-gon |
author_sort |
Perry George |
title |
Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease |
title_short |
Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease |
title_full |
Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease |
title_fullStr |
Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease |
title_full_unstemmed |
Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease |
title_sort |
ectopic localization of foxo3a protein in lewy bodies in lewy body dementia and parkinson's disease |
publisher |
BMC |
series |
Molecular Neurodegeneration |
issn |
1750-1326 |
publishDate |
2009-07-01 |
description |
<p>Abstract</p> <p>Lewy bodies and Lewy neurites constitute the cardinal neuropathological features of both Parkinson's disease (PD) and Lewy body dementia (LBD). Whereas α-synuclein has been found to be the major component of the Lewy body, the mechanisms by which neurons degenerate, as well as basic mechanisms involved in the formation of α-synuclein-related inclusions, remain obscure. We have suggested previously that potential mechanisms are likely to leave a "molecular signature" or protein adduct within the Lewy body, and have found examples of such signatures in previous studies. In this study, we demonstrate increased FOXO3 in association with Lewy bodies and Lewy neurites in LBD and PD brain tissue. Since FOXO proteins are involved in several pathways responsible for the regulation of cell death, cell proliferation, and cell metabolism, the ectopic localization of FOXO3 to Lewy bodies provides evidence that aberrations in basic cellular biochemistry may contribute to inclusion formation, which is likely more complex than a simple "gain of function" toxicity as is commonly opined. In light of the known interaction of FOXO3 and 14-3-3, basic protein-protein interaction between these proteins and α-synuclein may be key.</p> |
url |
http://www.molecularneurodegeneration.com/content/4/1/32 |
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