Departments of Biology, Bioengineering, and Medicinal Chemistry, University of Utah, Salt Lake City, UT, USA.
Methods Mol Biol. 2022;2303:807-820. doi: 10.1007/978-1-0716-1398-6_60.
Glycosaminoglycans (GAGs), belonging to a family of negatively charged linear polysaccharides, have been found in the cores of amyloid inclusions such as Lewy bodies, which are the central pathological features in Parkinson's disease (PD), a neurodegenerative disease. Lewy bodies/neurites are mostly composed of α-synuclein protein (α-syn) aggregates. Recent studies have shown that α-syn aggregates can propagate via neurons in a prion-like fashion by seeding the endogenous cellular α-syn. Various GAGs, especially heparan sulfate (HS), have been shown to be very critical in the aggregation of α-syn. HS chains of heparan sulfate proteoglycans (HSPGs) mediate the uptake of α-syn aggregates and help seed intracellular accumulation and further neuronal spread. Methods that inhibit the binding of these aggregates to HSPG have been shown to decrease the aggregate uptake and propagation. Here, we describe a cell-based assay to screen inhibitors of HS and α-syn interactions.
糖胺聚糖（GAGs）属于带负电荷的线性多糖家族，已在包括路易体在内的淀粉样蛋白核心中被发现，而路易体是帕金森病（PD）这种神经退行性疾病的主要病理学特征。路易体/神经突主要由α-突触核蛋白（α-syn）聚集体组成。最近的研究表明，α-syn 聚集体可以通过以朊病毒样方式接种内源性细胞 α-syn 在神经元中传播。各种 GAGs，特别是硫酸乙酰肝素（HS），已被证明在 α-syn 的聚集过程中非常关键。硫酸乙酰肝素蛋白聚糖（HSPG）的 HS 链介导 α-syn 聚集体的摄取，并有助于种子细胞内积累和进一步的神经元扩散。已证实抑制这些聚集体与 HSPG 结合的方法可减少聚集体的摄取和传播。在这里，我们描述了一种基于细胞的筛选 HS 和 α-syn 相互作用抑制剂的方法。
