p75 reduces β-amyloid-induced sympathetic innervation deficits in an Alzheimer's disease mouse model
p75 reduces β-amyloid-induced sympathetic innervation deficits in an Alzheimer's disease mouse model
复制标题
DOI：
10.1073/pnas.0901533106
复制
发表时间：
2009-05-12
影响因子：
11.1
通讯作者：
Lee, Kuo-Fen
中科院分区：
文献类型：
--
作者：
Bengoechea, Tasha G.;Chen, Zhijiang;Lee, Kuo-Fen
β-淀粉样蛋白（A β）对脑细胞有不良影响，但对其在阿尔茨海默病（AD）中对周围神经系统的影响知之甚少。几条体外证据表明，神经营养因子受体p75介导或加剧A β诱导的神经毒性。在这里，我们表明，p75缺陷的交感神经元更敏感的A β诱导的轴突生长抑制。为了研究p75在AD交感神经系统中的作用，将p75突变小鼠与AD模型小鼠杂交。大多数p75缺陷型AD小鼠在3周龄时死亡。致死性与多器官交感神经支配的严重缺陷有关。当在p75缺陷型AD小鼠中删除1个拷贝的编码A β产生所必需的蛋白质的BACE 1基因时，交感神经支配显著恢复。这些结果表明，p75对AD小鼠模型中的交感神经系统具有神经保护作用。
beta-Amyloid (A beta) has adverse effects on brain cells, but little is known about its effects on the peripheral nervous system in Alzheimer's disease ( AD). Several lines of in vitro evidence suggest that the neurotrophin receptor p75 mediates or exacerbates A beta-induced neurotoxicity. Here, we show that p75-deficient sympathetic neurons are more sensitive to A beta-induced neurite growth inhibition. To investigate the role of p75 in the sympathetic nervous system of AD, p75 mutant mice were crossed with a mouse line of AD model. The majority of p75-deficient AD mice died by 3 weeks of age. The lethality is associated with severe defects in sympathetic innervation to multiple organs. When 1 copy of the BACE1 gene encoding a protein essential in A beta production was deleted in p75-deficient AD mice, sympathetic innervation was significantly restored. These results suggest that p75 is neuroprotective for the sympathetic nervous system in a mouse model of AD.