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
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.
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.
Regulate glutamate homeostasis and affect excitotoxic neuronal damage in AD
Expressed in endothelial cell, neurons, astrocytes and microglia
Regulate glucose homeostasis in the brain Accelerate BBB breakdown, following secondary neurodegeneration caused by Aβ
Expressed in endothelial cells, pericytes, astrocytes, the choroid plexus and neurons
Transport of endoxenobiotics across the encephalon Involved in the clearance of Aβ from the brain into blood ABCB1 at the BBB declines during normal aging
  
Highly expressed in BBB endothelial cells
Mediates the cellular efflux of Aβ in HEK293 cells
Expressed in brain capillary endothelial cells, glial cells and neurons
Mediates 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]  
Widely expressed in brain tissues
Stimulates 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
    
Expressed in microglia, neurons, and brain endothelial cells
Mediates 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
    
Localized in brain endothelial cells, astrocytes and pericytes
Lack of ABCC1 could increase Aβ40 and Aβ42 levels compared to those in ABCC1-positive controls
Table 1 An overview of the SLC and ABC transporters in the brain, with the proposed relevance to AD pathology.
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