AN INVIVO MODEL FOR THE NEURODEGENERATIVE EFFECTS OF BETA-AMYLOID AND PROTECTION BY SUBSTANCE-P
AN INVIVO MODEL FOR THE NEURODEGENERATIVE EFFECTS OF BETA-AMYLOID AND PROTECTION BY SUBSTANCE-P
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DOI：
10.1073/pnas.88.16.7247
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发表时间：
1991-08-01
影响因子：
11.1
通讯作者：
YANKNER, BA
中科院分区：
文献类型：
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作者：
KOWALL, NW;BEAL, MF;YANKNER, BA
老年斑中β-淀粉样蛋白的沉积是阿尔茨海默病（AD）的病理标志。成年大鼠大脑皮层中β-淀粉样蛋白的局灶性沉积引起了深刻的神经退行性变化，包括神经元损失以及神经元和神经突的退化。 Alz-50 抗原的慢性诱导出现在 β-淀粉样蛋白局灶性皮质沉积物周围的神经元中。免疫印迹分析表明，β-淀粉样蛋白在大鼠大脑皮层中诱导出 Alz-50 免疫反应蛋白，该蛋白与 AD 患者大脑皮层中诱导的蛋白非常相似。当神经肽物质 P 与大脑皮层共同给药时，可以防止 β-淀粉样蛋白诱导的神经元损失和 Alz-50 蛋白的表达。全身施用 P 物质还可以防止脑内 β-淀粉样蛋白的影响。因此，β-淀粉样蛋白是成人大脑体内的一种强效神经毒素，其作用可以被 P 物质阻断。
Deposition of the beta-amyloid protein in senile plaques is a pathologic hallmark of Alzheimer disease (AD). Focal deposition of beta-amyloid in the adult rat cerebral cortex caused profound neurodegenerative changes, including neuronal loss and degenerating neurons and neurites. Chronic induction of the Alz-50 antigen appeared in neurons around focal cortical deposits of beta-amyloid. Immunoblot analysis showed that beta-amyloid induced Alz-50-immunoreactive proteins in rat cerebral cortex that were very similar to the proteins induced in human cerebral cortex from patients with AD. The neuropeptide substance P prevented beta-amyloid-induced neuronal loss and expression of Alz-50 proteins when coadministered into the cerebral cortex. Systemic administration of substance P also provided protection against the effects of intracerebral beta-amyloid. Thus, beta-amyloid is a potent neurotoxin in the adult brain in vivo, and its effects can be blocked by substance P.