葡萄糖转运蛋白1在阿尔茨海默病中的作用研究进展
2017-07-01李卫萍张磊申艳方杜菊梅
李卫萍+张磊+申艳方+杜菊梅
[摘要] 阿尔茨海默病(AD)是老年人最常见的痴呆类型,其发病率呈逐年增长趋势,目前发病机制尚未完全阐明,亦无有效的预防及治疗措施。葡萄糖转运蛋白1(GLUT1)是主要在血脑屏障内皮细胞表达的葡萄糖转运体,介导血液葡萄糖顺浓度梯度跨血脑屏障转运至脑组织,为脑组织细胞提供代谢所需能量。研究表明,GLUT1在AD患者血脑屏障内皮细胞表达减少,可能与AD发病机制及病理损害有关,笔者通过查阅近年来相关研究文献,系统总结了GLUT1在血脑屏障完整性破坏、Aβ清除障碍、Tau蛋白过度磷酸化等多个AD病理过程中的作用研究进展,以期为进一步探索GLUT1在AD中的确切作用机制实验研究提供参考。
[关键词] 阿尔茨海默病;葡萄糖转运蛋白1;β淀粉样蛋白;Tau蛋白磷酸化
[中图分类号] R742 [文献标识码] A [文章编号] 1673-7210(2017)05(b)-0036-04
[Abstract] Alzheimers disease (AD) is the most common type of dementia in the elderly. The incidence of Alzheimers disease is increasing year by year. At present, the pathogenesis of Alzheimers disease has not been fully elucidated and there is no effective preventive and therapeutic measures. Glucose transporter 1 (GLUT1) is a glucose transporter expressed mainly in the blood-brain barrier endothelial cells, which transports blood glucose to the brain tissue along the blood-brain barrier and provides energy for metabolism of brain cells. It is concluded that the expression of GLUT1 in the blood-brain barrier endothelial cells of AD patients is decreased, which may be related to the pathogenesis and pathological damage of AD. GLUT1 play a important role in the damage of blood-brain barrier integrity, amyloid β-peptide (Aβ) clearance and phosphorylation of tau. By reviewing relevant literatures in recent years, we hope to explore the GLUT1 in AD to provide a reference.
[Key words] Alzheimers disease; Glucose transporter 1; β-amyloid protein; Phosphorylation of Tau
阿爾茨海默病(Alzheimer disease,AD)是老年人常见的神经系统变性疾病,占老年痴呆的60%~80%,临床上以进行性认知和记忆功能障碍为主要表现。AD病理特征主要表现为β淀粉样蛋白异常沉积(β-amyloid,Aβ)形成老年斑、Tau蛋白过度磷酸化形成神经纤维缠结、神经元减少、脑内皮质小动脉淀粉样变性(cerebral amyloid angiopathy,CAA)等[1]。随着世界人口老龄化程度的逐步加剧,AD患病人数正以每20年增加一倍的速率增长[2],预计到2050年全球将有AD患者115 400万[3]。截至2010年中国AD患者已增至569万,患病率高达6.25‰[4],其中65岁以上人群中AD患病率为3.21%[5]。AD发病机制复杂,虽然相继提出了Aβ级联学说、衰老与氧化应激学说、Tau蛋白过度磷酸化学说、神经递质通道学说、胆碱能系统障碍等发病机制假说[6],但AD确切发病机制仍未完全阐明,目前尚无治疗或阻止AD病情进展的有效方法[7],使全世界AD防治面临严峻挑战。……
