ABSTRACT
There are several mechanisms by which molecules can be transported from the systemic circulation to the CNS: 1) simple diffusion, 2) facilitated diffusion, 3) active transport and 4) paracellular diffusion. Many factors, such as the size, charge and hydrophobicity determine the capability of molecules to move through the BBB (Liu-Synder and Webster 2006). The tight junctions between endothelial cells form a physical barrier by signifi cantly reducing passive diffusion, leading molecules to move predominantly across cells (transcellular pathway) (Fig. 2). Gases
such as oxygen and carbon dioxide and small lipophilic molecules can successfully diffuse across the barriers via the lipid membranes. The infl ux of small polar solutes, nutrients such as glucose and amino acids and the effl ux of waste products are controlled by specifi c solute transporters in cellular membranes. Potentially toxic products derived from the diet or the environment present in the circulation can be excluded by the BBB by several members of the ATP-binding cassette (ABC) transporter family. While the BBB expresses P-glycoprotein (P-gp, ABCB1), multidrugresistance related proteins (MRPs, ABCC family) and breast-cancer resistance protein (BCRP, ABCG2), the choroid plexus utilize ABCs and other type of transporters to control the traffi c of the substances. However, most drugs with the potential to be used in treating CNS diseases are substrates for ABC transporter family (Abbott et al. 2010). Both the BBB
and BCSFB constitute an important hurdle against the passage of larger molecules (i.e., peptides and proteins). However, some smaller peptides such as beta-amyloid (Aβ) that are substrates for transporters traffi c in and out through neuronal membranes (Abbott et al. 2010).
