ABC transporters at the blood–brain barrier

ABSTRACT

Introduction: The blood–brain barrier (BBB) possesses an outstanding ability to protect the brain against xenobiotics and potentially poisonous metabolites. Owing to this, ATP binding cassette (ABC) export proteins have garnered significant interest in the research community. These transport proteins are predominantly localized to the luminal membrane of brain microvessels, where they recognize a wide range of different substrates and transport them back into the blood circulation.

Areas covered: This review summarizes recent findings on these transport proteins, including their expression in the endothelial cell membrane and their substrate recognition. Signaling cascades underlying the expression and function of these proteins will be discussed as well as their role in diseases such as Alzheimer’s disease, epilepsy, amyotrophic lateral sclerosis and brain tumors.

Expert opinion: ABC transporters represent an integral part of the human transportome and are of particular interest at the blood–brain barrier they as they significantly contribute to brain homeostasis. In addition, they appear to be involved in myriad CNS diseases. Therefore studying their mechanisms of action as well as their signaling cascades and responses to internal and external stimuli will help us understand the pathogenesis of these diseases.

KEYWORDS:

• ABC proteins
• Alzheimer disease
• amytotrophic lateral sclerosis
• aryl hydrocarbon receptor
• blood–brain barrier
• breast cancer resistance protein
• multidrug resistance related proteins
• p-glycoprotein
• signaling
• pregnane-X receptor

Article highlights

• ABC export proteins including p-glycoprotein, breast cancer resistance protein and Mrp-proteins are highly expressed at the luminal side of brain capillary endothelial cells

• They recognize an abundancy of diverse compounds as substrates including

• cytostatic drugs, immunosuppressants, corticoids, opiates, HIV drugs, antiepileptics, antipsychotics, antibiotics, antidepressants and others

• ABC transporters in the BBB respond very sensitive to endogenous and external stimuli, underlining their pivotal role in CNS protection. They are regulated either by ligand-activated transcription factors (nuclear receptors) or by proteins, which signal to transcription factors and thus trigger the same process.

• Expression and/or function ABC transporters are either involved in or altered during the pathogenesis of various CNS diseases including epilepsy, brain tumors, CNS lymphoma, ischemic stroke, Alzheimer disease, Adrenoleuko-dystrophy, multiple sclerosis, Parkinson disease, ALS, lysosomal storage diseases, HIV related brain disorders, hippocampal sclerosis, Tangier disease, Stargardt disease and others

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.