Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL, 34243, USA.
J Mol Neurosci. 2013 Feb;49(2):270-6. doi: 10.1007/s12031-012-9866-6. Epub 2012 Aug 14.
Alzheimer's disease (AD) is a neurodegenerative process characterized, in part, by the accumulation of beta-amyloid proteins (Aβ) in the brain. Evidence now suggests that the excessive Aβ accumulation is the result of impaired clearance from the brain. Recent studies have indicated that retinoid X receptor (RXR) activation stimulates the metabolic clearance of Aβ and rapidly reverses Aβ-induced behavioral deficits, doing so in an apoE-dependent manner. Previously, we reported that soluble apoE (i.e., not bound to Aβ) facilitated Aβ transit across the blood-brain barrier (BBB). As Aβ clearance from the brain involves both metabolic and BBB-mediated processes, the current studies investigated the impact of RXR stimulation on Aβ clearance across the BBB. Treatment with RXR agonists increased Aβ clearance across the BBB both in vitro and in vivo. Moreover, this processes appeared to involve apoE as RXR agonism did not stimulate Aβ BBB clearance when apoE was absent. Thus, RXR activation could mitigate Aβ brain burden by promoting both the metabolic and BBB clearance of Aβ, offering a novel approach to the treatment of AD.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征部分在于大脑中β-淀粉样蛋白（Aβ）的积累。现在有证据表明，Aβ的过度积累是由于其从大脑中的清除受损所致。最近的研究表明，视黄醇 X 受体（RXR）的激活刺激 Aβ 的代谢清除，并迅速逆转 Aβ 引起的行为缺陷，这种作用是 apoE 依赖性的。之前，我们报告可溶性 apoE（即，未与 Aβ 结合）促进 Aβ 通过血脑屏障（BBB）的转运。由于 Aβ 从大脑中的清除涉及代谢和 BBB 介导的过程，因此目前的研究调查了 RXR 刺激对 Aβ 通过 BBB 清除的影响。RXR 激动剂的治疗在体外和体内均增加了 Aβ 通过 BBB 的清除。此外，这一过程似乎涉及 apoE，因为当 apoE 不存在时，RXR 激动剂不会刺激 Aβ 的 BBB 清除。因此，RXR 的激活可以通过促进 Aβ 的代谢和 BBB 清除来减轻 Aβ 在大脑中的负担，为 AD 的治疗提供了一种新方法。
