Efflux proteins at the blood–brain barrier: review and bioinformatics analysis

Abstract

1. Efflux proteins at the blood–brain barrier provide a mechanism for export of waste products of normal metabolism from the brain and help to maintain brain homeostasis. They also prevent entry into the brain of a wide range of potentially harmful compounds such as drugs and xenobiotics.

2. Conversely, efflux proteins also hinder delivery of therapeutic drugs to the brain and central nervous system used to treat brain tumours and neurological disorders. For bypassing efflux proteins, a comprehensive understanding of their structures, functions and molecular mechanisms is necessary, along with new strategies and technologies for delivery of drugs across the blood–brain barrier.

3. We review efflux proteins at the blood–brain barrier, classified as either ATP-binding cassette (ABC) transporters (P-gp, BCRP, MRPs) or solute carrier (SLC) transporters (OATP1A2, OATP1A4, OATP1C1, OATP2B1, OAT3, EAATs, PMAT/hENT4 and MATE1).

4. This includes information about substrate and inhibitor specificity, structural organisation and mechanism, membrane localisation, regulation of expression and activity, effects of diseases and conditions and the principal technique used for in vivo analysis of efflux protein activity: positron emission tomography (PET).

5. We also performed analyses of evolutionary relationships, membrane topologies and amino acid compositions of the proteins, and linked these to structure and function.

Keywords:

• ABC transporters
• bioinformatics analysis
• blood–brain barrier
• drug delivery
• efflux proteins
• neurological disorders
• PET imaging
• solute carriers

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Declaration of interest

The authors report no potential conflicts of interest. This work was supported by the Hamadan University of Medical Sciences and the University of Leeds.