Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease

Molecular Neurodegeneration

Hyoung-gon Lee⁴  Xiongwei Zhu⁴  Mark A Smith⁴  George Perry³  Rudy J Castellani¹  Atsushi Takeda⁵  Raymond Choi⁴  Eisaku Kondo²  Sandra L Siedlak⁴  Shu G Chen⁴  Xinglong Wang⁴  Haihua Liu⁴  Bo Su⁴ 

[1] Division of Neurology, Department of Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan;Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan;UTSA Neurosciences Institute and Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, Texas 78249, USA;Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA;Department of Pathology, University of Maryland, Baltimore, Maryland 21201, USA

Others  :  866117
DOI  :  10.1186/1750-1326-4-32

 received in 2009-06-04, accepted in 2009-07-23,  发布年份 2009

【 摘 要 】

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.

【 授权许可】

   
2009 Su et al; licensee BioMed Central Ltd.

【 图 表 】

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