Pilot study of the reducing effect on amyloidosis in vivo by three FDA pre-approved drugs via the Alzheimer's APP 5' untranslated region.
Pilot study of the reducing effect on amyloidosis in vivo by three FDA pre-approved drugs via the Alzheimer's APP 5' untranslated region.
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DOI：
10.2174/1567205053585855
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发表时间：
2005-03
影响因子：
2.1
通讯作者：
S. Tucker;Michelle Ahl;A. Bush;D. Westaway;Xudong Huang;J. Rogers
中科院分区：
文献类型：
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作者：
S. Tucker;Michelle Ahl;A. Bush;D. Westaway;Xudong Huang;J. Rogers
采用众所周知的阿尔茨海默病小鼠模型进行了一项试点研究，以评估三种FDA预先批准的药物的抗淀粉样蛋白功效。向TgCRND 8小鼠的饮用水提供帕罗西汀（SSRI和APP 5 'UTR导向的先导化合物）、N-乙酰半胱氨酸（抗氧化剂）和红霉素（大环内酯类抗生素）三个月。本报告提供了测量药物治疗和安慰剂动物中淀粉样蛋白Abeta-40和Abeta-42 Abeta的稳态水平的数据，以pmol Abeta/g小鼠脑皮质表示。在小鼠暴露于帕罗西汀（N=5）、NAC（N=7）和红霉素（N=7）后，相对于匹配的安慰剂对应物，A β肽水平的相对水平降低。这些结果证明了进一步筛选APP 5 'UTR靶标以鉴定在体内表现出抗淀粉样蛋白功效的新药的策略的概念验证。这些数据还表明帕罗西汀、NAC和红霉素具有统计学显著的抗淀粉样蛋白趋势。讨论了使用更大的TgCRND 8小鼠队列对这些化合物进行进一步研究的可能性。
A pilot study was conducted employing a well known mouse model for Alzheimer's disease to evaluate the anti-amyloid efficacy of three FDA pre-approved drugs. Paroxetine (SSRI and APP 5'UTR directed lead compound), N-acetyl cysteine (antioxidant), and erythromycin (macrolide antibiotic) were provided to the drinking water of TgCRND8 mice for three months. This report provides data that measured the steady-state levels of amyloid Abeta-40 and Abeta-42 Abeta as pmol Abeta per gram of mouse brain cortex in drug treated and placebo animals. The relative levels of Abeta peptide levels were reduced after exposure of mice to paroxetine (N=5), NAC (N=7), and erythromycin (N=7) relative to matched placebo counterparts. These results demonstrated proof-of concept for a strategy to further screen the APP 5'UTR target to identify novel drugs that exhibit anti-amyloid efficacy in vivo. These data also demonstrated a statistically significant anti-amyloid trend for paroxetine, NAC and erythromycin. The potential for conducting further studies with these compounds using larger cohorts of TgCRND8 mice is discussed.