Multidrug resistance-associated proteins: expression and function in the central nervous system

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Drug delivery to the central nervous system (CNS) is severely restricted by physiological barriers.
• The blood-brain barrier (BBB) and blood-cerebrospinal fluid (BCSFB) barrier are primary obstacles, featuring tight junctions that limit paracellular transport.
• These barriers also express ATP-dependent efflux transporters, such as multidrug resistance-associated proteins (MRPs), which actively reduce drug accumulation.

Purpose of the Study:

• To review current knowledge on brain drug distribution barriers.
• To explore the emerging concept of brain parenchyma acting as a secondary barrier to drug permeation.
• To highlight the clinical significance of MRP transporter expression in neurological disorders.

Main Methods:

• Literature review of recent research on CNS drug delivery.
• Analysis of the role of efflux transporters in brain parenchyma.
• Examination of MRP transporter expression in neurological conditions.

Main Results:

• The BBB and BCSFB act as primary barriers to CNS drug entry.
• Brain parenchyma cells may function as a secondary barrier through efflux transporter expression.
• These primary and secondary barriers cooperate to limit xenobiotic accumulation in the CNS.

Conclusions:

• Drug distribution in the CNS is a complex process involving multiple, coordinated barriers.
• MRP transporters are crucial in both barrier tissues and brain parenchyma, influencing drug disposition.
• Understanding these barriers and transporters is vital for developing effective CNS therapeutics for neurological disorders.