Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate.
Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate.
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DOI：
10.1002/syn.21967
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发表时间：
2017-07
期刊：
影响因子：
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通讯作者：
Schapira AHV
中科院分区：
文献类型：
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作者：
Migdalska-Richards A;Ko WKD;Li Q;Bezard E;Schapira AHV
糖脑苷酶1(GBA1)基因突变与帕金森病(PD)和高谢病(GD)有关。在这两种情况下，这种情况都与葡萄糖脑苷酶(GCase)缺乏有关，GCase是由GBA1编码的酶。氨溴索是一种小分子伴侣，在小鼠身上已被证明可以穿越血脑屏障，增加GCase活性，降低α-突触核蛋白水平。在这项研究中，我们分析了氨溴索治疗对健康的非人灵长类动物GCase活性的影响。我们发现，每天服用氨溴索会导致大脑GCase活性增加。我们的工作进一步表明，氨溴索应作为一种治疗帕金森病和神经病理性GD的新疗法进行研究。
Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood‐brain barrier, increase GCase activity and reduce alpha‐synuclein protein levels. In this study, we analyze the effect of ambroxol treatment on GCase activity in healthy nonhuman primates. We show that daily administration of ambroxol results in increased brain GCase activity. Our work further indicates that ambroxol should be investigated as a novel therapy for both PD and neuronopathic GD in humans.