Basic research for clinical treatment of neuropathic Gaucher disease by chemical chhaperones

高谢病的神经系统表现尚无有效的治疗方法。我们发现N-辛基-β-valienamine(NOV)能提高F213I突变型Gba在培养细胞中的蛋白水平和酶活性。我们曾尝试建立表达F213I蛋白的小鼠模型，但未能成功。评价NOV对正常小鼠的作用。未见不良反应，组织中GBA活性随NOV剂量增加而升高。我们还发现了新的化合物，双环诺吉霉素类似物，在突变的GBA上显示出化学伴侣活性。

There are no effective treatment for neurological manifestations in Gaucher disease. We found N-octyl-β-valienamine (NOV) could increase the protein level and enzyme activity of F213I mutant GBA in culture cells. We have tried to establish a model mouse expressing F213I protein, but failed to establish the mice. The NOV effects on normal mice were evaluated. No adverse effect was observed and GBA activity increased with increasing NOV dose in tissues. We also found new compounds, bicyclic nojirimycin analogues, show a chemical chaperone activity on mutant GBAs.