Wang Peipei, Ding Kan
Glycobiology and Glycochemistry Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Protein Pept Lett. 2014;21(10):1048-56. doi: 10.2174/0929866521666140626095145.
Misfolded protein amyloid-beta protein (Aβ) and tau protein are two high hallmarks of Alzheimer's disease (AD), representing significant targets in treating AD. Researches on mechanisms of the two proteins inducing neuron dysfunctions provide therapeutic strategies of AD, including inhibition of Aβ production and aggregation, acceleration of Aβ clearance as well as reduction of tau hyperphosphorylation. Proteoglycans (PGs) consist of a core protein and glycosaminoglycans (GAGs) chains, with enormous structural diversity due to variation in the core protein, the number of GAGs chains as well as extent and position of sulfation. Considerable evidences have indicated that PGs and GAGs play important roles in Aβ and tau processing. Numbers of GAGs and analogues have potential therapeutic function in AD. In this Review, we focus on the relationship of PGs and GAGs with misfolded proteins in AD and their potential therapeutic implications.
错误折叠的蛋白质——淀粉样β蛋白（Aβ）和tau蛋白是阿尔茨海默病（AD）的两个主要标志，是治疗AD的重要靶点。对这两种蛋白诱导神经元功能障碍机制的研究为AD提供了治疗策略，包括抑制Aβ的产生和聚集、加速Aβ的清除以及减少tau蛋白的过度磷酸化。蛋白聚糖（PGs）由一个核心蛋白和糖胺聚糖（GAGs）链组成，由于核心蛋白的差异、GAGs链的数量以及硫酸化的程度和位置不同，其结构具有巨大的多样性。大量证据表明，PGs和GAGs在Aβ和tau蛋白的处理过程中发挥着重要作用。许多GAGs及其类似物在AD中具有潜在的治疗功能。在本综述中，我们重点关注PGs和GAGs与AD中错误折叠蛋白的关系及其潜在的治疗意义。
