PGP and amyotrophic lateral sclerosis: To mitigate this damage, astrocytes signal to the endothelial cells to upregulate the multidrug resistance transporter ABCB1 (P-Glycoprotein) (P-gp), which can also modulate glutamate levels.94,95 While vital to reducing excitotoxicity, the effectiveness of Riluzole is limited by the upregulation of the P-gp seen in ALS.80,94,96 Appropriate P-gp levels are necessary to achieve therapeutic benefits of most pharmaceuticals,97 thus, the BCNSB integrity should be a primary target for all future therapies for ALS.