Terawaki Seigo, Nakanishi Hiroki, Shibuya Toko, Sakai Norio, Otomo Takanobu
Department of Molecular and Genetic Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan.
Lipidome Lab Co., Ltd., Akita 010-0825, Japan.
Int J Mol Sci. 2025 Jun 29;26(13):6275. doi: 10.3390/ijms26136275.
Lysosomal storage diseases are caused by defective lysosomal function, such as impaired lysosomal enzyme activities, which include more than 70 different diseases. Although biomarkers and therapies have been developed to date for some of them, many others remain challenging to diagnose and treat. In this study, an elevated level of Globotriaosylsphingosine (Lyso-Gb3), an already known biomarker for Fabry disease, was confirmed in the knock-out cells of the , , and genes and models for Fabry, mucolipidosis II/III (ML II/III), and combined saposin deficiency, respectively. Lyso-Gb3 was high in ML II/III patient skin fibroblasts compared with normal cells and was decreased after total lysosomal enzyme supplementation. There have been no useful biomarkers reported in ML II/III until now. This study shows that Lyso-Gb3 is elevated in ML II/III patient cells and is decreased by treatment, indicating that Lyso-Gb3 is a potential biomarker for ML II/III.
溶酶体贮积症是由溶酶体功能缺陷引起的，如溶酶体酶活性受损，这类疾病有70多种。尽管目前已经为其中一些疾病开发了生物标志物和治疗方法，但许多其他疾病的诊断和治疗仍然具有挑战性。在本研究中，分别在法布里病、黏脂贮积症II/III（ML II/III）和鞘磷脂激活蛋白联合缺乏症的基因敲除细胞及模型中，证实了作为法布里病已知生物标志物的球三糖基鞘氨醇（Lyso-Gb3）水平升高。与正常细胞相比，ML II/III患者皮肤成纤维细胞中的Lyso-Gb3含量较高，在补充总溶酶体酶后降低。到目前为止，ML II/III中尚未报道有用的生物标志物。本研究表明，Lyso-Gb3在ML II/III患者细胞中升高，并且通过治疗降低，这表明Lyso-Gb3是ML II/III的潜在生物标志物。
