Laboratoire CRRET, EAC/CNRS, Université Paris Est Créteil Val de Marne, Faculté des Sciences et Technologie, France.
Curr Protein Pept Sci. 2011 May;12(3):258-68. doi: 10.2174/138920311795860188.
A number of neurodegenerative diseases, as Parkinson, prion, and Alzheimer's diseases, has been directly associated with altered conformations of certain peptides or proteins that assemble to form highly organized aggregates, also called amyloid fibers. Glycosaminoglycans have shown to play important roles on fibrils formation, stability and resistance to proteolysis. This manuscript reviews from basic concepts on the biochemistry and biology of glycosaminoglycans to their implications in neurodegeneration with particular emphasis in pathologic protein aggregation. Prion protein, Aβ42, Tau, and α-synuclein, are all proteins that can interact with glycosaminoglycans. We document here how these interactions may modify protein conformation, aggregation kinetics, and fibers stabilization with important consequences in disease. We also raise questions which answers may make advance the understanding of the implication of GAGs in neurodegeneration.
许多神经退行性疾病，如帕金森病、朊病毒病和阿尔茨海默病，都与某些肽或蛋白质的构象改变直接相关，这些肽或蛋白质会组装成高度有序的聚集体，也称为淀粉样纤维。糖胺聚糖已被证明在原纤维形成、稳定性和抗蛋白水解方面发挥着重要作用。本文从糖胺聚糖的生物化学和生物学的基本概念综述到其在神经退行性变中的意义，特别强调了病理性蛋白聚集。朊病毒蛋白、Aβ42、Tau 和 α-突触核蛋白都是可以与糖胺聚糖相互作用的蛋白质。我们在这里记录了这些相互作用如何改变蛋白质构象、聚集动力学和纤维稳定性，这对疾病有重要影响。我们还提出了一些问题，这些问题的答案可能会加深我们对 GAGs 在神经退行性变中的作用的理解。
