The role of ABCB1 and ABCA1 in beta-amyloid clearance at the neurovascular unit in Alzheimer's disease.

The role of ABCB1 and ABCA1 in beta-amyloid clearance at the neurovascular unit in Alzheimer's disease.
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DOI:
10.3389/fphys.2013.00045
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发表时间:
2013
影响因子:
4
通讯作者:
Rivest S
Rivest S
中科院分区:
医学2区
文献类型:
--
作者:
Elali A;Rivest S

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阿尔茨海默病(AD)是一种影响老年人的进行性神经退行性疾病,随着年龄的增长而发展,达到严重的认知障碍。淀粉样蛋白沉积和神经纤维缠结构成AD的主要病理标志。淀粉样蛋白沉积是由β-淀粉样蛋白(Aβ)肽在大脑中的过度产生和积累引发的。神经血管单位(NVU)的功能障碍被认为是AD发展的原因,因为Aβ从大脑中的清除受损。形成NVU的细胞表达几种三磷酸腺苷ATP结合盒(ABC)转运蛋白,其中ABCB 1和ABCA 1在Aβ加工中起重要作用。药物转运蛋白ABCB 1直接将Aβ从大脑转运到血液循环中,而胆固醇转运蛋白ABCA 1以载脂蛋白E(ApoE)依赖性方式中和Aβ聚集能力,促进Aβ随后从大脑中消除。在本小综述中,我们将总结NVU中ABCB 1和ABCA 1在Aβ清除中的作用。此外,我们将概述和讨论ABCB 1和ABCA 1在NVU介导Aβ从大脑中有效清除的可能合作。
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects elderly persons, evolving with age to reach severe cognitive impairment. Amyloid deposits and neurofibrillary tangles constitute the main pathological hallmarks of AD. Amyloid deposits are initiated by the excessive production and accumulation of beta-amyloid (Aβ) peptides in the brain. The dysfunction of the Neurovascular Unit (NVU) has been proposed to be causative in AD development, due to an impaired clearance of Aβ from the brain. Cells forming the NVU express several Adenosine Triphosphate ATP-Binding Cassette (ABC) transporters, among which ABCB1 and ABCA1 play an important role in Aβ processing. The drug transporter ABCB1 directly transports Aβ from the brain into the blood circulation, whereas the cholesterol transporter ABCA1 neutralizes Aβ aggregation capacity in an Apolipoprotein E (ApoE)-dependent manner, facilitating Aβ subsequent elimination from the brain. In the present minireview, we will summarize the contribution of ABCB1, and ABCA1 at the NVU in Aβ clearance. Moreover, we will outline and discuss the possible collaboration of ABCB1, and ABCA1 at the NVU in mediating an efficient clearance of Aβ from the brain.
缺乏周细胞会导致内皮增生和异常血管形态发生。
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