Blood-Brain Barrier P-Glycoprotein Function in Neurodegenerative Disease
Affiliation: Department of Neurology, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
Keywords: Blood-brain barrier, P-glycoprotein, [11C]-verapamil PET, Parkinson, Alzheimer, Microglia, pesticides, olfactory neurons, progressive supranuclear palsy (PSP), mutation
Protection of the brain is strengthened by active transport and ABC transporters. P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a substrate from the brain, which is important for maintaining loco-regional homeostasis in the brain and protection against toxic compounds. Importantly, dysfunctional BBB P-gp transport is postulated as an important factor contributing to accumulation of aggregated protein in neurodegenerative disorders such as Alzheimers disease (AD) and Parkinsons disease (PD). Furthermore, P-gp is a major factor in mediating resistance to brain entry of numerous exogenous compounds, including toxins that can be involved in PD pathogenesis. This review highlights the role of altered P-gp function in the pathogenesis and progression of neurodegenerative disease. Also the implications of alterations in P-gp function for the treatment of these diseases are discussed.
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