The Research Institute of the McGill University Health Centre, Department of Medicine, McGill University, Montreal, QC, Canada.
Neuroscience. 2010 Jan 20;165(2):427-35. doi: 10.1016/j.neuroscience.2009.10.033.
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.
阿尔茨海默病（AD）是老年人群中最常见的痴呆症形式，是一种不可治愈的神经退行性疾病，其特征是记忆力丧失。在这里，我们使用 AD 大鼠模型来研究 caprospinol 的体内疗效，caprospinol 是一种基于减少 AD 大脑中 22R-羟胆固醇合成会增加β-淀粉样蛋白神经毒性这一概念开发的疾病修饰性类固醇。caprospinol 治疗患病大鼠，可通过 Morris 水迷宫测试评估，减轻记忆障碍。这种认知功能的恢复伴随着海马淀粉样沉积、星形胶质细胞增生、神经退行性变和 Tau 蛋白磷酸化的减少。在平行研究中，发现正常大鼠前脑中 caprospinol 的生物利用度取决于治疗的剂量和持续时间，这表明该化合物能够穿过血脑屏障。这些结果表明 caprospinol 是一种有前途的 AD 治疗候选药物。
