Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease.
Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease.
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DOI：
10.1186/1750-1326-4-32
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发表时间：
2009-07-23
影响因子：
15.1
通讯作者：
Lee HG
中科院分区：
文献类型：
--
作者：
Su B;Liu H;Wang X;Chen SG;Siedlak SL;Kondo E;Choi R;Takeda A;Castellani RJ;Perry G;Smith MA;Zhu X;Lee HG
路易体和路易神经突构成帕金森病（PD）和路易体痴呆（LBD）的主要神经病理特征。虽然α-突触核蛋白已被发现是路易体的主要成分，但神经元退化的机制以及与α-突触核蛋白相关的包涵体形成的基本机制仍然不清楚。我们以前曾提出，潜在的机制可能会在路易体内留下一个“分子签名”或蛋白质加合物，并在以前的研究中发现了这种签名的例子。在这项研究中，我们证明了增加FOXO 3与路易体和路易神经突在LBD和PD脑组织。由于FOXO蛋白参与了负责调节细胞死亡、细胞增殖和细胞代谢的几种途径，FOXO 3异位定位于路易体提供了基础细胞生物化学中的畸变可能有助于包涵体形成的证据，这可能比通常认为的简单的“功能获得”毒性更复杂。根据FOXO 3和14-3-3的已知相互作用，这些蛋白质与α-突触核蛋白之间的碱性蛋白质-蛋白质相互作用可能是关键。
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.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
2.5
作者：
Castellani, RJ;Perry, G;Smith, MA
通讯作者：
Smith, MA
DOI：
10.1093/jnen/61.3.245
发表时间：
2002-03-01
影响因子：
3.2
作者：
Kawamoto, Y;Akiguchi, I;Budka, H
通讯作者：
Budka, H
影响因子：
14.5
作者：
GIBB, WRG;ESIRI, MM;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
12.7
作者：
Castellani, RJ;Siedlak, SL;Smith, MA
通讯作者：
Smith, MA