Blood-brain barrier transporters: An overview of function, dysfunction in Alzheimer's disease and strategies for treatment

Juliana C S Chaves; Samantha J Dando; Anthony R White; Lotta E Oikari

doi:10.1016/j.bbadis.2023.166967

Blood-brain barrier transporters: An overview of function, dysfunction in Alzheimer's disease and strategies for treatment

Biochim Biophys Acta Mol Basis Dis. 2024 Feb;1870(2):166967. doi: 10.1016/j.bbadis.2023.166967. Epub 2023 Nov 24.

Authors

Juliana C S Chaves¹, Samantha J Dando², Anthony R White¹, Lotta E Oikari³

Affiliations

¹ Mental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, QUT, Brisbane, QLD, Australia.
² Centre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia.
³ Mental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, QUT, Brisbane, QLD, Australia. Electronic address: Lotta.Oikari@qimrberghofer.edu.au.

PMID: 38008230
DOI: 10.1016/j.bbadis.2023.166967

Abstract

The blood-brain-barrier (BBB) has a major function in maintaining brain homeostasis by regulating the entry of molecules from the blood to the brain. Key players in BBB function are BBB transporters which are highly expressed in brain endothelial cells (BECs) and critical in mediating the exchange of nutrients and waste products. BBB transporters can also influence drug delivery into the brain by inhibiting or facilitating the entry of brain targeting therapeutics for the treatment of brain disorders, such as Alzheimer's disease (AD). Recent studies have shown that AD is associated with a disrupted BBB and transporter dysfunction, although their roles in the development in AD are not fully understand. Modulation of BBB transporter activity may pose a novel approach to enhance the delivery of drugs to the brain for enhanced treatment of AD. In this review, we will give an overview of key functions of BBB transporters and known changes in AD. In addition, we will discuss current strategies for transporter modulation for enhanced drug delivery into the brain.

Keywords: Alzheimer's diseases; BBB disruption; BBB modulation; BBB transporters; Blood-brain-barrier (BBB); Drug delivery.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / drug therapy
Blood-Brain Barrier*
Brain
Endothelial Cells
Humans
Membrane Transport Proteins

Substances

Membrane Transport Proteins