The impact of ATP-binding cassette transporters in the diseased brain: Context matters.
The impact of ATP-binding cassette transporters in the diseased brain: Context matters.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Amsterdam, NL · Author affiliation
Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.Location evidence
Heemstede, NL · Author affiliation
Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Neuroscience, Department of (Neuro)Pathology, Amsterdam, the Netherlands; Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, the Netherlands.Location evidence
Minneapolis, US · Author affiliation
Brain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.Location evidence
Vienna, AT · Author affiliation
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.Location evidence
Hannover, DE · Author affiliation
Translational Neuropharmacology Lab, NIFE, Department of Experimental Otology of the ENT Clinics, Hannover Medical School, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.Location evidence
US · Author affiliation · country only
Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.Location evidence
Utrecht, NL · Author affiliation
Department of Pathology, Amsterdam University Medical Centers, Amsterdam, the Netherlands; Laboratory for Childhood Cancer Pathology, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.Location evidence
Manchester, GB · Author affiliation
Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Faculty of Biology, Medicine and Health, University of Manchester; The Christie NHS Foundation Trust, Manchester, UK. Electronic address: m.d.gooijer@nki.nl.Location evidence
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Original abstract
ATP-binding cassette (ABC) transporters facilitate the movement of diverse molecules across cellular membranes, including those within the CNS. While most extensively studied in microvascular endothelial cells forming the blood-brain barrier (BBB), other CNS cell types also express these transporters. Importantly, disruptions in the CNS microenvironment during disease can alter transporter expression and function. Through this comprehensive review, we explore the modulation of ABC transporters in various brain pathologies and the context-dependent consequences of these changes. For instance, downregulation of ABCB1 may exacerbate amyloid beta plaque deposition in Alzheimer's disease and facilitate neurotoxic compound entry in Parkinson's disease. Upregulation may worsen neuroinflammation by aiding chemokine-mediated CD8 T cell influx into multiple sclerosis lesions. Overall, ABC transporters at the BBB hinder drug entry, presenting challenges for effective pharmacotherapy. Understanding the context-dependent changes in ABC transporter expression and function is crucial for elucidating the etiology and developing treatments for brain diseases.