Modulation of the ATP-Binding Cassette B1 Transporter by Neuro-Inflammatory Cytokines: Role in the Pathogenesis of Alzheimer's Disease.

Abstract

Inflammation of neuronal tissue, or neuro-inflammation, is associated with neurological diseases, including Alzheimer's disease (AD) (Patel et al., 2005; Walters et al., 2016; Wang B. et al., 2016). The exact role of neuro-inflammation in AD remains uncertain as it may be a result of other causative factors in AD, but can subsequently contribute to the course of the disease, or be caused by other factors. Neuro-inflammation is significantly correlated with changes in the expression of brain proteins that regulate the transport or signaling pathways of endogenous and exogenous molecules (Tilleux and Hermans, 2007; Kim et al., 2015; Gao et al., 2017). ATP-binding cassette (ABC) proteins, such as ABCB1 (P-glycoprotein, P-gp), are highly expressed in the brain capillary endothelial cells of the blood - brain barrier (BBB) and limit the uptake of certain endogenous and exogenous compounds into the brain (Loscher and Potschka, 2005; Zhang et al., 2015). Several studies have reported alterations in the expression and functions of ABCB1 in AD models (Wijesuriya et al., 2010; van Assema et al., 2012). The formation of amyloid beta (Aβ) (a substrate of ABCB1) plaques in the brain is a histological hallmark associated with AD (Lee et al., 2004; Wildburger et al., 2017). The ABCB1 transporter removes Aβ from the brain into the circulatory system (Hartz et al., 2010; ElAli and Rivest, 2013). Thus, alterations in the expression or function of ABCB1 may affect the progression of AD. The role of ABCB1 in AD progression and treatment has been recently reviewed, elsewhere (Pahnke et al., 2014; Sita et al., 2017). However, the focus of this opinion article is to discuss the effects of neuro-inflammatory cytokines on ABCB1 function and their role in the pathogenesis of AD.