Abstract
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 disease, P-glycoprotein.
Current Pharmaceutical Design
Title:Targeting CNS Transporters for Treatment of Neurodegenerative Diseases
Volume: 20 Issue: 10
Author(s): Gabriele Jedlitschky, Markus Grube, Igor Mosyagin, Heyo K. Kroemer and Silke Vogelgesang
Affiliation:
Keywords: ABC transporters, Alzheimer’s disease, beta amyloid, blood-brain barrier, neurodegeneration, organic anion transporters, parkinson’s disease, P-glycoprotein.
Abstract: 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.
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Cite this article as:
Jedlitschky Gabriele, Grube Markus, Mosyagin Igor, Kroemer K. Heyo and Vogelgesang Silke, Targeting CNS Transporters for Treatment of Neurodegenerative Diseases, Current Pharmaceutical Design 2014; 20 (10) . https://dx.doi.org/10.2174/13816128113199990460
DOI https://dx.doi.org/10.2174/13816128113199990460 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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