Molecular transporters that are expressed in brain, especially at the blood-brain barrier (BBB), are increasingly recognized as
possible therapeutic targets in the treatment of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Some
ATP-binding cassette (ABC) transporters, particularly P-glycoprotein (ABCB1), MRP1 (ABCC1) and BCRP (ABCG2), have been implicated
in the clearance of neurotoxic polypeptides that characteristically accumulate in the brain, such as amyloid-β (Aβ) peptides in Alzheimer’s
disease. Several lines of evidence also implicate lipid transporters of the A-branch of ABC transporters in pathogenesis. Induction
of transporters via the activation of specific nuclear receptors may represent a novel approach to restoring diminished BBB function.
On the other hand, transporters in the brain capillary endothelium regulate the permeation of therapeutic compounds into the brain. In addition
to the export pumps that limit brain entry of exogenous substances, SLC-type uptake transporters, especially of the OCT
(SLC22A) family, are of potential relevance in that they mediate not only the uptake of several drugs used for the treatment of neurodegenerative
diseases, but also of certain neurotoxins. Here, we summarize recent findings and novel strategies targeting transporters to reduce
brain pathology or to improve drug therapy.
Keywords: ABC transporters, Alzheimer’s disease, beta amyloid, blood-brain barrier, neurodegeneration, organic anion transporters, parkinson’s
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