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ATP结合盒转运蛋白在阿尔茨海默病中的功能与表达

The Function and Expression of ATP-Binding Cassette Transporters Proteins in the Alzheimer's Disease.

作者信息

Aykac Asli, Sehirli Ahmet Özer

机构信息

Department of Biophysics, Near East University, Nicosia, Cyprus.

Department of Pharmacology, Faculty of Dentistry, Near East University, Nicosia, Cyprus.

出版信息

Glob Med Genet. 2021 Sep 17;8(4):149-155. doi: 10.1055/s-0041-1735541. eCollection 2021 Dec.

Abstract

Despite many years of research, radical treatment of Alzheimer's disease (AD) has still not been found. Amyloid-β (Aβ) peptide is known to play an important role in the pathogenesis of this disease. AD is characterized by three main changes occurring in the central nervous system: (1) Aβ plaque accumulation that prevents synaptic communication, (2) the accumulation of hyperphosphorylated tau proteins that inhibit the transport of molecules inside neurons, and (3) neuronal cell loss of the limbic system. Mechanisms leading to Aβ accumulation in AD are excessive Aβ production as a result of mutations in amyloid precursor protein or genes, and impairment of clearance of Aβ due to changes in Aβ aggregation properties and/or Aβ removal processes. Human ATP-binding cassette (ABC) transporters are expressed in astrocyte, microglia, neuron, brain capillary endothelial cell, choroid plexus, choroid plexus epithelial cell, and ventricular ependymal cell. ABC transporters have essential detoxification and neuroprotective roles in the brain. The expression and functional changes in ABC transporters contribute to the accumulation of Aβ peptide. In conclusion, the review was aimed to summarize and highlight accumulated evidence in the literature focusing on the changing functions of human ABC transporter members, in AD pathogenesis and progression.

摘要

尽管经过多年研究,但仍未找到阿尔茨海默病(AD)的根治方法。已知淀粉样β(Aβ)肽在该疾病的发病机制中起重要作用。AD的特征是中枢神经系统发生的三个主要变化:(1)Aβ斑块积聚,阻止突触通讯;(2)过度磷酸化的tau蛋白积聚,抑制神经元内分子的运输;(3)边缘系统的神经元细胞丢失。导致AD中Aβ积聚的机制是淀粉样前体蛋白或基因发生突变导致Aβ产生过多,以及由于Aβ聚集特性和/或Aβ清除过程的变化而导致Aβ清除受损。人类ATP结合盒(ABC)转运蛋白在星形胶质细胞、小胶质细胞、神经元、脑毛细血管内皮细胞、脉络丛、脉络丛上皮细胞和脑室室管膜细胞中表达。ABC转运蛋白在大脑中具有重要的解毒和神经保护作用。ABC转运蛋白的表达和功能变化有助于Aβ肽的积聚。总之,本综述旨在总结和突出文献中积累的证据,重点关注人类ABC转运蛋白成员在AD发病机制和进展中的功能变化。

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