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肝素寡糖作为老年痴呆症的潜在治疗药物。

Heparin oligosaccharides as potential therapeutic agents in senile dementia.

作者信息

Ma Qing, Cornelli Umberto, Hanin Israel, Jeske Walter P, Linhardt Robert J, Walenga Jeanine M, Fareed Jawed, Lee John M

机构信息

Department of Pharmacology and Experimental Therapeutics, Stritch School ofMedicine, Loyola University Chicago, Maywood, IL 60153, USA.

出版信息

Curr Pharm Des. 2007;13(15):1607-16. doi: 10.2174/138161207780765918.

Abstract

Heparin is a glycosaminoglycan mixture currently used in prophylaxis and treatment of thrombosis. Heparin possesses non-anticoagulant properties, including modulation of various proteases, interactions with fibroblast growth factors, and anti-inflammatory actions. Senile dementia of Alzheimer's type is accompanied by inflammatory responses contributing to irreversible changes in neuronal viability and brain function. Vascular factors are also involved in the pathogenesis of senile dementia. Inflammation, endogenous proteoglycans, and assembly of senile plagues and neurofibrillary tangles contribute directly and indirectly to further neuronal damage. Neuron salvage can be achieved by anti-inflammation and the competitive inhibition of proteoglycans accumulation. The complexity of the pathology of senile dementia provides numerous potential targets for therapeutic interventions designed to modulate inflammation and proteoglycan assembly. Heparin and related oligosaccharides are known to exhibit anti-inflammatory effects as well as inhibitory effects on proteoglycan assembly and may prove useful as neuroprotective agents.

摘要

肝素是一种糖胺聚糖混合物,目前用于血栓形成的预防和治疗。肝素具有非抗凝特性,包括对各种蛋白酶的调节、与成纤维细胞生长因子的相互作用以及抗炎作用。阿尔茨海默病型老年痴呆症伴有炎症反应,导致神经元活力和脑功能发生不可逆变化。血管因素也参与老年痴呆症的发病机制。炎症、内源性蛋白聚糖以及老年斑和神经原纤维缠结的形成直接或间接导致进一步的神经元损伤。通过抗炎和竞争性抑制蛋白聚糖积累可以实现神经元挽救。老年痴呆症病理的复杂性为旨在调节炎症和蛋白聚糖组装的治疗干预提供了众多潜在靶点。已知肝素和相关寡糖具有抗炎作用以及对蛋白聚糖组装的抑制作用,可能被证明是有用的神经保护剂。

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