Departments of Biological Sciences and Cell and Developmental Biology, Kennedy Center for Research on Human Development, Vanderbilt University Station B, Nashville, TN 37232, USA.
Neural Plast. 2012;2012:124548. doi: 10.1155/2012/124548. Epub 2012 May 20.
Fragile X syndrome (FXS) is the most common known genetic form of intellectual disability and autism spectrum disorders. FXS patients suffer a broad range of other neurological symptoms, including hyperactivity, disrupted circadian activity cycles, obsessive-compulsive behavior, and childhood seizures. The high incidence and devastating effects of this disease state make finding effective pharmacological treatments imperative. Recently, reports in both mouse and Drosophila FXS disease models have indicated that the tetracycline derivative minocycline may hold great therapeutic promise for FXS patients. Both models strongly suggest that minocycline acts on the FXS disease state via inhibition of matrix metalloproteinases (MMPs), a class of zinc-dependent extracellular proteases important in tissue remodeling and cell-cell signaling. Recent FXS clinical trials indicate that minocycline may be effective in treating human patients. In this paper, we summarize the recent studies in Drosophila and mouse FXS disease models and human FXS patients, which indicate that minocycline may be an effective FXS therapeutic treatment, and discuss the data forming the basis for the proposed minocycline mechanism of action as an MMP inhibitor.
脆性 X 综合征（FXS）是最常见的已知遗传性智力障碍和自闭症谱系障碍。FXS 患者还患有广泛的其他神经症状，包括多动、昼夜活动周期紊乱、强迫行为和儿童期癫痫发作。这种疾病状态的高发病率和破坏性影响使得寻找有效的药物治疗方法势在必行。最近，在小鼠和果蝇 FXS 疾病模型中的报告表明，四环素衍生物米诺环素可能对 FXS 患者具有很大的治疗潜力。这两种模型都强烈表明，米诺环素通过抑制基质金属蛋白酶（MMPs）来作用于 FXS 疾病状态，MMPs 是一类锌依赖性细胞外蛋白酶，在组织重塑和细胞间信号传递中起着重要作用。最近的 FXS 临床试验表明，米诺环素可能对治疗人类患者有效。本文总结了果蝇和小鼠 FXS 疾病模型以及人类 FXS 患者的最新研究，这些研究表明米诺环素可能是一种有效的 FXS 治疗方法，并讨论了作为 MMP 抑制剂的米诺环素作用机制的基础数据。
