Department of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico II, Via S. Pansini n. 5, 80131 Naples, Italy.
Biochim Biophys Acta Mol Basis Dis. 2019 Nov 1;1865(11):165539. doi: 10.1016/j.bbadis.2019.165539. Epub 2019 Aug 26.
Heparan sulfate proteoglycans (HSPGs) are complex carbohydrate-modified proteins ubiquitously expressed on cell surfaces, extracellular matrix and basement membrane of mammalian tissues. Beside to serve as structural constituents, they regulate multiple cellular activities. A critical involvement of HSPGs in development has been established, and perturbations of HSPG-dependent pathways are associated with many human diseases. Recent evidence suggest a role of HSPGs in the pathogenesis of mucopolysaccharidoses (MPSs) where the accumulation of undigested HS results in the loss of cellular functions, tissue damage and organ dysfunctions accounting for clinical manifestations which include central nervous system (CNS) involvement, degenerative joint disease and reduced bone growth. Current therapies are not curative but only ameliorate the disease symptoms. Here, we highlight the link between HSPG functions in the development of CNS and musculoskeletal structures and the etiology of some MPS phenotypes, suggesting that HSPGs may represent potential targets for the therapy of such incurable diseases.
硫酸乙酰肝素蛋白聚糖（HSPGs）是广泛表达于哺乳动物组织细胞表面、细胞外基质和基底膜的一种复杂的碳水化合物修饰蛋白。除了作为结构成分外，它们还调节多种细胞活动。HSPGs 在发育中的关键作用已经得到确立，并且 HSPG 依赖性途径的扰动与许多人类疾病有关。最近的证据表明，HSPGs 在黏多糖贮积症（MPS）的发病机制中起作用，未消化的 HS 的积累导致细胞功能丧失、组织损伤和器官功能障碍，从而导致包括中枢神经系统（CNS）受累、退行性关节病和骨骼生长减少在内的临床表现。目前的治疗方法不是治愈性的，只能改善疾病症状。在这里，我们强调了 HSPG 在中枢神经系统和肌肉骨骼结构发育以及某些 MPS 表型病因中的作用，表明 HSPGs 可能是治疗这些不治之症的潜在靶点。
