Biology Department, Concordia University, Montreal, QC H4B 1R6, Canada.
BH Bioscience, Montreal, QC H3W 2L2, Canada.
Molecules. 2020 Nov 23;25(22):5477. doi: 10.3390/molecules25225477.
Autosomal dominant polycystic kidney disease (ADPKD) causes progressive cystic degeneration of the renal tubules, the nephrons, eventually severely compromising kidney function. ADPKD is incurable, with half of the patients eventually needing renal replacement. Treatments for ADPKD patients are limited and new effective therapeutics are needed. Melatonin, a central metabolic regulator conserved across all life kingdoms, exhibits oncostatic and oncoprotective activity and no detected toxicity. Here, we used the () model of polycystic kidney disease to test the cyst-reducing potential of melatonin. Significant cyst reduction was found in the renal (Malpighian) tubules upon melatonin administration and suggest mechanistic sophistication. Similar to vertebrate PKD, the fly PKD model responds to the antiproliferative drugs rapamycin and mimics of the second mitochondria-derived activator of caspases (Smac). Melatonin appears to be a new cyst-reducing molecule with attractive properties as a potential candidate for PKD treatment.
常染色体显性多囊肾病（ADPKD）导致肾小管、肾单位的进行性囊性变性，最终严重损害肾功能。ADPKD 无法治愈，一半的患者最终需要肾脏替代治疗。ADPKD 患者的治疗方法有限，需要新的有效治疗方法。褪黑素是一种在所有生命领域都保守的中枢代谢调节剂，具有抗肿瘤和抗肿瘤保护活性，且未检测到毒性。在这里，我们使用多囊肾病的 () 模型来测试褪黑素的减少囊肿的潜力。褪黑素给药后，在肾脏（马耳他）小管中发现明显的囊肿减少，并提示其机制复杂。与脊椎动物 PKD 相似，果蝇 PKD 模型对增殖抑制剂雷帕霉素和第二线粒体衍生的半胱天冬酶激活剂（Smac）模拟物有反应。褪黑素似乎是一种新的减少囊肿的分子，具有作为 PKD 治疗候选药物的吸引力。
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