Novel Molecular Biomarkers at the Blood-Brain Barrier in ALS
Figure 1
The molecular mechanism of ALS pathology in astrocytes. WT astrocyte (left) contains a balanced ratio of Kir4.1 and AQP4 channels in its cell membrane that also forms the endfeet around the endothelial layer of the blood vessel (center). ALS astrocyte (right) shows a misbalance of channel molecules with an abundance of AQP4 over Kir4.1. This causes swelling of endfeet and affects the BBB that becomes leaky for immune factors such as immunoglobulins (IgGs) that are known to cause intracellular calcium spikes (red trace and the pseudocolor image of a Ca2+-sensitive dye at the peak of the response in cultured astrocytes) and may start excitotoxic processes in situ. Colored panels in the bottom illustrate immunocytochemistry of AQP4 and GFAP in WT versus ALS astrocytes in the rat brain while the panels with traces illustrate whole-cell Kir currents from WT versus ALS astrocytes in culture and two examples of respective Western blot bands for Kir protein.
