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Aging and disease    2020, Vol. 11 Issue (2) : 390-404     DOI: 10.14336/AD.2019.0519
Review Article |
Alteration in the Function and Expression of SLC and ABC Transporters in the Neurovascular Unit in Alzheimer’s Disease and the Clinical Significance
Yongming Jia1, Na Wang2, Yingbo Zhang3, Di Xue1, Haoming Lou4,*, Xuewei Liu1,*
1Department of Neuropharmacology, College of Pharmacy, Qiqihar Medical University, Qiqihar, China
2Department of Pathophysiology, Basic Medical Science College, Qiqihar Medical University, Qiqihar, China
3College of Pathology, Qiqihar Medical University, Qiqihar, China
4Department of Medicinal Chemistry and Chemistry of Chinese Materia Medica, School of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
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Abstract  

The neurovascular unit (NVU) plays an important role in maintaining the function of the central nervous system (CNS). Emerging evidence has indicated that the NVU changes function and molecules at the early stage of Alzheimer’s disease (AD), which initiates multiple pathways of neurodegeneration. Cell types in the NVU have become attractive targets in the interventional treatment of AD. The NVU transportation system contains a variety of proteins involved in compound transport and neurotransmission. Brain transporters can be classified as members of the solute carrier (SLC) and ATP-binding cassette (ABC) families in the NVU. Moreover, the transporters can regulate both endogenous toxins, including amyloid-beta (Aβ) and xenobiotic homeostasis, in the brains of AD patients. Genome-wide association studies (GWAS) have identified some transporter gene variants as susceptibility loci for late-onset AD. Therefore, the present study summarizes changes in blood-brain barrier (BBB) permeability in AD, identifies the location of SLC and ABC transporters in the brain and focuses on major SLC and ABC transporters that contribute to AD pathology.

Keywords blood-brain barrier      ATP-binding cassette transporters      solute carrier      Alzheimer’s disease     
Corresponding Authors: Lou Haoming,Liu Xuewei   
About author:

These authors contributed equally to this work.

Just Accepted Date: 05 June 2019   Issue Date: 13 March 2020
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Jia Yongming
Wang Na
Zhang Yingbo
Xue Di
Lou Haoming
Liu Xuewei
Cite this article:   
Jia Yongming,Wang Na,Zhang Yingbo, et al. Alteration in the Function and Expression of SLC and ABC Transporters in the Neurovascular Unit in Alzheimer’s Disease and the Clinical Significance[J]. Aging and disease, 2020, 11(2): 390-404.
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http://www.aginganddisease.org/EN/10.14336/AD.2019.0519     OR
Figure 1.  SLC and ABC transporters in the NVU.
TransporterLocationFunctionReferences
EAAT1/2Expressed in astrocytesRegulate glutamate homeostasis and affect excitotoxic neuronal damage in AD[40]
GLUT1Expressed in endothelial cell, neurons, astrocytes and microgliaRegulate glucose homeostasis in the brain
Accelerate BBB breakdown, following secondary neurodegeneration caused by Aβ
[52]
[60]
ABCB1Expressed in endothelial cells, pericytes, astrocytes, the choroid plexus and neuronsTransport of endoxenobiotics across the encephalon
Involved in the clearance of Aβ from the brain into blood ABCB1 at the BBB declines during normal aging
[83]
[85] [90]
ABCG2Highly expressed in BBB endothelial cellsMediates the cellular efflux of Aβ in HEK293 cells[103]
ABCG4Expressed in brain capillary endothelial cells, glial cells and neuronsMediates the efflux of cholesterol to form apoE-containing lipoprotein
Suppresses ABCG1 and ABCG4 function and increases Aβ secretion Mediates the cellular efflux of Aβ in HEK293 cells stably transfected with mouse abcg4
[109, 110]
[111] [103]
ABCA1Widely expressed in brain tissuesStimulates the efflux of cholesterol and phospholipid to ApoE
Increased ABCA1 levels induced by LXR ligands can increase the secreted Aβ concentration Decreases the influx of Aβ across the BBB Regulates the levels of ApoE and ApoE lipidation ABCA1 rs2422493 (C-477T) polymorphism are associated with increasing AD risk
[113]
[118] [117] [119] [126]
ABCA7Expressed in microglia, neurons, and brain endothelial cellsMediates the transfer of phospholipids and cholesterol across cell membranes
Inhibits Aβ secretion without affecting the activities of α- and β-secretases Plays roles in APP processing, leading to enhanced Aβ secretion Phagocytic Aβ clearance in microglia is reduced in Abca7-/- mice ABCA7 SNPs are relate to the occurrence of AD
[132]
[132] [133] [136] [145]
ABCC1Localized in brain endothelial cells, astrocytes and pericytesLack of ABCC1 could increase Aβ40 and Aβ42 levels compared to those in ABCC1-positive controls[153]
Table 1  An overview of the SLC and ABC transporters in the brain, with the proposed relevance to AD pathology.
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