van Horssen Jack, Wesseling Pieter, van den Heuvel Lambert P W J, de Waal Robert M W, Verbeek Marcel M
Department of Pathology, University Medical Center, Nijmegen, Netherlands.
Lancet Neurol. 2003 Aug;2(8):482-92. doi: 10.1016/s1474-4422(03)00484-8.
Proteoglycans are associated with all kinds of amyloid deposits in the human body. These complex macromolecules, in particular heparan sulphate proteoglycans, have also been implicated in several features of the pathogenesis of Alzheimer's disease (AD), including the genesis of senile plaques, cerebrovascular amyloid, and neurofibrillary tangles. In this review we focus on the role of proteoglycans and glycosaminoglycans in amyloidogenesis in general and in AD in particular. Heparan sulphate proteoglycans may promote amyloid-beta peptide (Abeta) or tau fibrillisation on the one hand, and provide resistance against proteolytic breakdown on the other. Knowledge about the role of proteoglycans in AD pathology may eventually be of therapeutic use, because small polysulphated compounds, which can interfere with the interaction between proteoglycan and Abeta, have been shown to stop or even prevent amyloidogenesis.
蛋白聚糖与人体内的各种淀粉样沉积物相关。这些复杂的大分子,尤其是硫酸乙酰肝素蛋白聚糖,也与阿尔茨海默病(AD)发病机制的若干特征有关,包括老年斑的形成、脑血管淀粉样变和神经原纤维缠结。在本综述中,我们重点关注蛋白聚糖和糖胺聚糖在一般淀粉样变形成,尤其是在AD中的作用。硫酸乙酰肝素蛋白聚糖一方面可能促进β淀粉样肽(Aβ)或tau蛋白纤维化,另一方面提供抗蛋白水解降解的能力。了解蛋白聚糖在AD病理中的作用最终可能具有治疗用途,因为已证明能干扰蛋白聚糖与Aβ之间相互作用的小多硫酸化化合物可阻止甚至预防淀粉样变形成。