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Renin inhibitor aliskiren exerts neuroprotection against amyloid beta-peptide toxicity in rat cortical neurons

机译:肾素抑制剂阿利吉仑对大鼠皮质神经元的淀粉样β肽毒性具有神经保护作用

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摘要

Accumulation of amyloid β-peptide (Aβ) in senile plaques, a pathological hallmark of Alzheimer's disease (AD), has been implicated in neuronal degeneration. Renin-angiotensin system (RAS) blockers, including the renin inhibitor aliskiren, are a group of clinically relevant anti-hypertensive agents. The present study was initiated to investigate whether aliskiren may modulate Aβ neurotoxicity as an additional function aside from its established property of lowering blood pressure. We found aliskiren conferred neuronal resistance to Aβ toxicity in primary rat cortical cultures. Moreover, both Aβ25-35 and Aβ1-42 induced renin expression in cortical neurons; in parallel, a heightened expression of renin was detected in the cerebral cortices of 9-month-old AD transgenic mice. Notably, aliskiren blocked Aβ-mediated neuronal induction of renin. We therefore concluded that aliskiren may carry neuroprotective action against Aβ toxicity. Furthermore, the aliskiren effects may involve downregulation of renin expression induced by Aβ.
机译:淀粉样蛋白β肽(Aβ)在老年斑中的积累是阿尔茨海默氏病(AD)的病理特征,与神经元变性有关。肾素-血管紧张素系统(RAS)阻滞剂,包括肾素抑制剂阿利吉仑,是一组与临床相关的降压药。本研究开始以研究阿利吉仑是否可以调节Aβ神经毒性作为其既定的降血压特性之外的附加功能。我们发现阿利吉仑在原代大鼠皮层培养物中赋予了对Aβ毒性的神经元抗性。此外,Aβ25-35和Aβ1-42均可诱导皮质神经元中肾素的表达。平行地,在9个月大的AD转基因小鼠的大脑皮层中检测到肾素的表达升高。值得注意的是,阿利吉仑阻断了Aβ介导的肾素神经元诱导作用。因此,我们得出结论,阿利吉仑可能具有抗Aβ毒性的神经保护作用。此外,阿利吉仑效应可能涉及下调由Aβ引起的肾素表达。

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