PDF(Pubmed)
Abstract：
Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice (UNT) to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.
摘要：
IVA型粘多糖贮积症（MPSIVA；MorquioA综合征）是一种罕见的常染色体隐性遗传溶酶体贮积症（LSD），由水解酶缺乏引起，N-乙酰半乳糖胺-6-硫酸盐硫酸酯酶,临床特征主要是肌肉骨骼表现。人类骨骼受累的机制通常是使用侵入性技术如骨活检来探索的。这使得人类的分析变得复杂。我们在野生型和MPSIVA敲除小鼠（UNT）中使用DDA和SWATH-MS比较了骨蛋白质组，以获得有关该疾病的机制信息。我们的发现揭示了基因敲除小鼠中超过1000种失调的蛋白质，包括那些与氧化磷酸化有关的，氧化应激（活性氧），DNA损伤,和铁运输，并提示乳酸脱氢酶可能是一个有用的预后和随访生物标志物。确定反映MPSIVA临床过程的生物标志物，严重程度,和进展对疾病管理有重要意义。
