Lee Michael H, Sahota Amrik, Ward Michael D, Goldfarb David S
NYU Langone Medical Center, New York, NY, USA,
Curr Rheumatol Rep. 2015 May;17(5):33. doi: 10.1007/s11926-015-0510-7.
Cystinuria is a genetic disease marked by recurrent kidney stone formation, usually at a young age. It frequently leads to chronic kidney disease. Treatment options for cystinuria have been limited despite comprehensive understanding of its genetic pathophysiology. Currently available therapies suffer from either poor clinical adherence to the regimen or potentially serious adverse effects. Recently, we employed atomic force miscopy (AFM) to identify L-cystine dimethylester (CDME) as an effective molecular imposter of L-cystine, capable of inhibiting crystal growth in vitro. More recently, we demonstrated CDME's efficacy in inhibiting L-cystine crystal growth in vivo utilizing a murine model of cystinuria. The application of AFM to discover inhibitors of crystal growth through structural mimicry suggests a novel approach to preventing and treating crystal diseases.
胱氨酸尿症是一种遗传性疾病,其特征是反复形成肾结石,通常在年轻时发病。它经常导致慢性肾病。尽管对其遗传病理生理学有全面的了解,但胱氨酸尿症的治疗选择一直有限。目前可用的疗法要么临床对治疗方案的依从性差,要么有潜在的严重不良反应。最近,我们利用原子力显微镜(AFM)鉴定出L-胱氨酸二甲酯(CDME)是L-胱氨酸的一种有效分子模拟物,能够在体外抑制晶体生长。最近,我们利用胱氨酸尿症小鼠模型证明了CDME在体内抑制L-胱氨酸晶体生长的功效。通过结构模拟应用AFM来发现晶体生长抑制剂,为预防和治疗晶体疾病提出了一种新方法。