The binding of HSA to astrocyte TGFBR1 and TGFBR2 fol lowing BBB disruption is associated with seizures in sev eral neurological diseases. HSA mediated astrocyte activation has been studied based on the up regulation selleck catalog of glial fibrillary acidic protein, an intermediate filament protein that maintains mechanical strength of the astrocytes. Up regulation of GFAP affects potassium and glutamate regulation by astrocytes. Increased potassium and glutamate concentration in the vicinity of neurons causes neuronal death, leading to sei zures caused by a reorganization of neuronal networks in the brain. Figure 2c links this interaction to astrocyte dysfunction and neuronal damage. Discussion This work aims at integrating host parasite, host host and parasite parasite PPI from multitude of sources and using them to study the pathogenesis of CM.

Despite a large corpus of literature on P. falciparum and human PPI from both experimental and theoretical sources, the in vivo significance of most of these PPI is not known. Since each PPI dataset has been derived using different experi mental and theoretical methods, the interactions were initially treated as de contextualized pairs of protein associations. GO annotation filters were then applied to the PPI data, which resulted in a set of host parasite PPI that are most likely to influence CM pathogenesis. This filtering is dependent on the currently available GO annotations for the various parasite and host proteins, and as a result important protein interaction pairs could also get filtered out.

The resulting PPI were then mapped to the key events PfEMP1 presentation, platelet activa tion and astrocyte damage resulting in a smaller, focused PPI set. Several established PPI not directly involved in these three key events get excluded. For instance, the interaction between PfEMP1 and CD36, which though responsible for increased cytoadherence, is filtered out as this event occurs only after PfEMP1 presentation. The sequestration of pRBCs to the EC through the sur face adhesion receptors is crucial to CM, since this directly affects BBB structure and function. This process is known to occur mainly through interactions between the P. falciparum protein PfEMP1 and human proteins present on endothelial cells. PfEMP1 presentation is thus a key event in the sequestration process. Brefeldin_A Though KAHRP and ETRAMP are crucial in PfEMP1 presentation, the effect of temperature on the trafficking of these proteins by PfHsps is not fully understood. This work links inter actions involving a set of PfHsps that might play a crucial role in the trafficking of ETRAMP and KAHRP to increased PfEMP1 presentation on the pRBCs. In CM, the effect of temperature in the trafficking of PfEMP1 to pRBC surface has been well studied.