N-terminal region of myelin basic protein reduces fibrillar amyloid-β deposition in Tg-5xFAD mice.
N-terminal region of myelin basic protein reduces fibrillar amyloid-β deposition in Tg-5xFAD mice.
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DOI：
10.1016/j.neurobiolaging.2014.10.006
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发表时间：
2015-02
影响因子：
4.2
通讯作者：
Van Nostrand WE
中科院分区：
文献类型：
--
作者：
Ou-Yang MH;Xu F;Liao MC;Davis J;Robinson JK;Van Nostrand WE
阿尔茨海默病（Alzheimer's disease，AD）是一种进行性神经退行性疾病，其特征是纤维状淀粉样蛋白β（Aβ）在脑内广泛沉积。以前，髓鞘碱性蛋白（MBP）被鉴定为Aβ原纤维形成的有效抑制剂，并且这种抑制活性定位于N-末端残基1-64，称为MBP 1的片段。在这里，我们发现，适度的神经元表达的融合蛋白的生物活性MBP 1片段和增强型绿色荧光蛋白（MBP 1-EGFP）显着改善的表现，空间学习记忆的Tg-5xFAD小鼠，病理性Aβ在大脑中的积累模型。在双基因Tg-5xFAD/Tg-MBP 1-EGFP小鼠中，不溶性Aβ和纤维状淀粉样蛋白的水平显著降低。定量体视学分析表明，淀粉样蛋白的减少是由于纤维斑块的大小减少，而不是斑块数量减少。目前的研究结果支持了先前的研究，表明MBP 1在体外抑制Aβ原纤维形成，并证明了MBP 1减少Aβ病理学和改善行为表现的能力。
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by extensive deposition of fibrillar amyloid β (Aβ) in the brain. Previously, myelin basic protein (MBP) was identified to be a potent inhibitor to Aβ fibril formation and this inhibitory activity was localized to the N-terminal residues 1–64, a fragment designated MBP1. Here we show that modest neuronal expression of a fusion protein of the biologically active MBP1 fragment and the enhanced green fluorescent protein (MBP1-EGFP) significantly improved the performance of spatial learning memory in Tg-5xFAD mice, a model of pathologic Aβ accumulation in brain. The levels of insoluble Aβ and fibrillar amyloid were significantly reduced in bigenic Tg-5xFAD/Tg-MBP1-EGFP mice. Quantitative stereological analysis revealed that the reduction in amyloid was due to a reduction in the size of fibrillar plaques, rather than a decrease in plaque numbers. The current findings support previous studies showing that MBP1 inhibits Aβ fibril formation in vitro, and demonstrate the ability of MBP1 to reduce Aβ pathology and improve behavioral performance.
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影响因子：
15.1
作者：
Kayed R;Head E;Sarsoza F;Saing T;Cotman CW;Necula M;Margol L;Wu J;Breydo L;Thompson JL;Rasool S;Gurlo T;Butler P;Glabe CG
通讯作者：
Glabe CG
DOI：
10.1073/pnas.0712197105
发表时间：
2008-02-19
影响因子：
11.1
作者：
Buxbaum, Joel N.;Ye, Zhengyi;Bartfai, Tamas
通讯作者：
Bartfai, Tamas
影响因子：
2.9
作者：
Hoos, Michael D.;Ahmed, Mahiuddin;Smith, Steven O.;Van Nostrand, William E.
通讯作者：
Van Nostrand, William E.
影响因子：
64.8
作者：
De Strooper, B;Saftig, P;Van Leuven, F
通讯作者：
Van Leuven, F
影响因子：
4.2
作者：
Bartzokis, G;Sultzer, D;Cummings, JL
通讯作者：
Cummings, JL