Department of Public Health and Caring Sciences, Molecular Geriatrics, University of Uppsala, Uppsala, Sweden.
Prog Mol Biol Transl Sci. 2010;93:309-34. doi: 10.1016/S1877-1173(10)93013-5.
Amyloidosis is a generic term for a group of diseases characterized by deposits in different organ systems of insoluble materials composed mainly of distinct fibrillar proteins named amyloid. Besides amyloid, heparan sulfate proteoglycan (HSPG), is commonly found in most amyloid deposits, suggesting that HS/HSPG may be functionally involved in the pathogenesis of amyloidosis. HS or HSPG is found to interact with a number of amyloid proteins, displaying a promoting effect on amyloid fibrilization in vitro. In addition, HS is reported to be involved in processing amyloid precursor proteins and mediate amyloid toxicity. Although little is known about the in vivo mechanisms regarding the codeposition of HS with amyloid proteins in different amyloid diseases, experiments carried out in animal models, especially in transgenic mouse model where HS molecular structure is modified, support an active role for HS in amyloidogenesis. Further experimental evidence is required to strengthen these in vivo findings at a molecular level. Animal models that express mutant forms of HS due to knockout of the enzymes involved in glycosaminoglycan (GAG) biosynthesis are expected to provide valuable tools for studying the implications of HS, as well as other GAGs, in amyloid disorders.
淀粉样变性是一组疾病的通用术语，其特征是在不同的器官系统中沉积不溶性物质，这些物质主要由不同的纤维状蛋白质组成，命名为淀粉样蛋白。除了淀粉样蛋白外，硫酸乙酰肝素蛋白聚糖（HSPG）通常也存在于大多数淀粉样沉积物中，这表明 HS/HSPG 可能在淀粉样变性的发病机制中具有功能作用。HS 或 HSPG 被发现与许多淀粉样蛋白相互作用，在体外显示出促进淀粉样纤维形成的作用。此外，HS 被报道参与淀粉样前体蛋白的加工，并介导淀粉样毒性。尽管对于不同淀粉样疾病中 HS 与淀粉样蛋白共沉积的体内机制知之甚少，但在动物模型中进行的实验，特别是在 HS 分子结构被修饰的转基因小鼠模型中，支持 HS 在淀粉样蛋白生成中的积极作用。需要进一步的实验证据来加强这些体内发现的分子水平。由于参与糖胺聚糖（GAG）生物合成的酶被敲除而表达突变形式 HS 的动物模型有望为研究 HS 以及其他 GAG 在淀粉样蛋白紊乱中的意义提供有价值的工具。
