Journal Article

The Interplay of ABC Transporters in Aβ Translocation and Cholesterol Metabolism: Implicating Their Roles in Alzheimer’s Disease

Sehgal, Aayush, Behl, Tapan, Bungau, Simona, Kaur, Ishnoor, Kumar, Arun, Uddin, Md. Sahab

2021

Overview

The occurrence of Alzheimer’s disease (AD) worldwide has been progressively accelerating at an alarming rate, without any successful therapeutic strategy for the disease mitigation. The complexity of AD pathogenesis needs to be targeted with an alternative approach, as provided by the superfamily of ATP-binding cassette (ABC) transporters, which constitutes an extensive range of proteins, capable of transporting molecular entities across biological membranes. These protein moieties have been implicated in AD, based upon their potential in lipid transportation, resulting in maintenance of cholesterol homeostasis. These transporters have been reported to target the primary hallmark of AD pathogenesis, namely, beta-amyloid hypothesis, which is associated with accumulation of beta-amyloid (Aβ) plaques in AD patients. The ABC transporters have been observed to be localized to the capillary endothelial cells of the blood-brain barrier and neural parenchymal cells, where they exhibit different roles, consequently influencing the neuronal expression of Aβ peptides. The review highlights different families of ABC transporters, ABCB1 (P-glycoprotein), ABCA (ABCA1, ABCA2, and ABCA7), ABCG2 (BCRP; breast cancer resistance protein), ABCG1 and ABCG4, as well as ABCC1 (MRP; multidrug resistance protein) in the CNS, and their interplay in regulating cholesterol metabolism and Aβ peptide load in the brain, simultaneously exerting protective effects against neurotoxic substrates and xenobiotics. The authors aim to establish the significance of this alternative approach as a novel therapeutic target in AD, to provide the researchers an opportunity to evaluate the potential aspects of ABC transporters in AD treatment.

• Publisher: Springer US,Springer Nature B.V
• Subject: ABC transporters / ABCA1 protein / Alzheimer Disease - drug therapy / Alzheimer Disease - metabolism / Alzheimer's disease / Amyloid beta-Peptides - metabolism / Animals / ATP-Binding Cassette Transporters - metabolism / ATP-binding protein / Biomedical and Life Sciences / Biomedicine / Blood-brain barrier / Brain - metabolism / Brain - pathology / Breast cancer / Cell Biology / Cholesterol / Cholesterol - metabolism / Endothelial cells / Homeostasis / Humans / Lipid metabolism / Metabolism / Models, Biological / Multidrug resistance / Neurobiology / Neurodegenerative diseases / Neurology / Neurosciences / Neurotoxicity / P-Glycoprotein / Pathogenesis / Protein transport / Proteins / Senile plaques / Therapeutic targets / Xenobiotics / β-Amyloid