CAPROSPINOL REDUCES AMYLOID DEPOSITS AND IMPROVES COGNITIVE FUNCTION IN A RAT MODEL OF ALZHEIMER'S DISEASE
CAPROSPINOL REDUCES AMYLOID DEPOSITS AND IMPROVES COGNITIVE FUNCTION IN A RAT MODEL OF ALZHEIMER'S DISEASE
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DOI：
10.1016/j.neuroscience.2009.10.033
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发表时间：
2010-01-20
期刊：
影响因子：
3.3
通讯作者：
Papadopoulos, V.
中科院分区：
文献类型：
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作者：
Lecanu, L.;Rammouz, G.;Papadopoulos, V.
阿尔茨海默病（AD）是老年人痴呆症中最常见的一种，是一种无法治愈的退行性神经系统疾病，其特征是记忆丧失。在这里，我们使用 AD 大鼠模型来研究 Caprospinol 的体内功效，Caprospinol 是一种缓解疾病的类固醇，其开发理念是减少 AD 大脑中 22R-羟基胆固醇的合成会增加 β-淀粉样蛋白神经毒性。根据莫里斯水迷宫测试的评估，Caprospinol 治疗患病大鼠可减轻记忆障碍。认知功能的恢复伴随着海马淀粉样蛋白沉积、星形胶质细胞增生、神经变性和 Tau 蛋白磷酸化的减少。在平行研究中，发现正常大鼠前脑中的卡普罗匹诺生物利用度取决于治疗的剂量和持续时间，证明了该化合物穿过血脑屏障的能力。这些结果使卡普罗匹醇成为治疗 AD 的有前途的候选药物。 (C) 2010 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Alzheimer's disease (AD), the most prominent form of dementia in elderly, is a yet incurable degenerative neurological illness characterized by memory loss. Here, we used an AD rat model to investigate the in vivo efficacy of caprospinol, a disease-modifying steroid developed on the concept that reduced synthesis of 22R-hydroxycholesterol in the AD brain increases beta-amyloid neurotoxicity. Caprospinol treatment of diseased rats attenuated memory impairment, as assessed using Morris watermaze tests. This recovery of cognitive function was accompanied by a reduction in hippocampal amyloid deposits, astrogliosis, neurodegeneration and Tau protein phopshorylation. In parallel studies, caprospinol bioavailability in normal rat forebrain was found to be dependent on the dose and duration of the treatment, demonstrating the ability of the compound to cross the blood-brain barrier. These results position caprospinol as a promising drug candidate for AD treatment. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.