Abnormal post-translational and extracellular processing of brevican in plaque-bearing mice over-expressing APPsw.
Abnormal post-translational and extracellular processing of brevican in plaque-bearing mice over-expressing APPsw.
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DOI：
10.1111/j.1471-4159.2010.06647.x
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发表时间：
2010-05
影响因子：
4.7
通讯作者：
Gottschall PE
中科院分区：
文献类型：
--
作者：
Ajmo JM;Bailey LA;Howell MD;Cortez LK;Pennypacker KR;Mehta HN;Morgan D;Gordon MN;Gottschall PE
阿尔茨海默病受试者前脑中淀粉样蛋白-β的聚集可能会干扰调节神经和突触可塑性的细胞外微环境的分子组织。蛋白聚糖是这种细胞外环境的主要成分。为了检验淀粉样蛋白-β或另一种淀粉样蛋白前体蛋白依赖性机制改变细胞外蛋白聚糖的积累和/或周转的假设，我们检查了在作为阿尔茨海默病模型的淀粉样蛋白-β沉积转基因小鼠（APPsw）的脑中，短蛋白聚糖（一种丰富的细胞外、携带硫酸软骨素的蛋白聚糖）的表达和加工是否改变。与非转基因小鼠相比，在携带淀粉样蛋白-β沉积的APPsw小鼠的海马组织中，附着于短蛋白聚糖的硫酸软骨素链的分子大小较小，可能是由于硫酸软骨素链的变化。此外，主要的蛋白水解片段的短蛋白聚糖的丰度显着减少，从几个端脑区域的APPsw小鼠相比，非转基因小鼠的提取物，但这些免疫反应性片段似乎积累邻近的斑块边缘。这些结果表明，淀粉样蛋白-β或淀粉样蛋白前体蛋白对负责蛋白聚糖合成和周转的蛋白水解切割机制发挥抑制作用。由于蛋白聚糖稳定突触结构并抑制分子可塑性，在携带淀粉样蛋白-β的小鼠和潜在的终末期人类阿尔茨海默病中观察到的缺陷性短蛋白聚糖加工可能导致神经可塑性缺陷。
Aggregation of amyloid-β in the forebrain of Alzheimer's disease subjects may disturb the molecular organization of the extracellular microenvironment that modulates neural and synaptic plasticity. Proteoglycans are major components of this extracellular environment. To test the hypothesis that amyloid-β, or another amyloid precursor protein dependent mechanism modifies the accumulation and/or turnover of extracellular proteoglycans, we examined whether the expression and processing of brevican, an abundant extracellular, chondroitin sulfate-bearing proteoglycan, were altered in brains of amyloid-β-depositing transgenic mice (APPsw) as a model of Alzheimer's disease. The molecular size of chondroitin sulfate chains attached to brevican was smaller in hippocampal tissue from APPsw mice bearing amyloid-β deposits compared to non-transgenic mice, likely due to changes in the chondroitin sulfate chains. Also, the abundance of the major proteolytic fragment of brevican was markedly diminished in extracts from several telencephalic regions of APPsw mice compared to non-transgenic mice, yet these immunoreactive fragments appeared to accumulate adjacent to the plaque edge. These results suggest that amyloid-β or amyloid precursor protein exert inhibitory effects on proteolytic cleavage mechanisms responsible for synthesis and turnover of proteoglycans. Since proteoglycans stabilize synaptic structure and inhibit molecular plasticity, defective brevican processing observed in amyloid-β-bearing mice and potentially end-stage human Alzheimer's disease, may contribute to deficient neural plasticity.
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影响因子：
11.2
作者：
Lee, JM;Yin, KJ;Xu, J
通讯作者：
Xu, J
DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
4.8
作者：
Flood, C;Gustafsson, M;Borén, J
通讯作者：
Borén, J
DOI：
10.1142/9781860947179_0004
发表时间：
2005-01-01
期刊：
MATRIX METALLOPROTEINASES IN THE CENTRAL NERVOUS SYSTEM
影响因子：
--
作者：
Gottschall, P. E.;Sandy, J. D.;Zimmermann, D. R.
通讯作者：
Zimmermann, D. R.
影响因子：
16.2
作者：
HSIAO, KK;BORCHELT, DR;CARLSON, G
通讯作者：
CARLSON, G