Figure 2

Schematic representation of the interactions between inflammatory processes and APP processing. Aβ generation by BACE1 and γ-secretase induces an inflammatory response, which involves the activation of microglia and astrocytes and the release of pro-inflammatory cytokines. This inflammatory response could be enhanced by brain trauma or by PS1 mutations, probably also by increased Aβ production. Inflammatory cytokines have been involved in the aggregation of Aβ [121]. Moreover, cytokines can affect the expression of secretases and APP, influencing their transcription, translation and/or activation [122]. Non-steroidal anti-inflammatory drug treatment could reverse the effect of inflammation on BACE1 transcription, modulate the cleavage site of γ-secretase and decrease the secretion of cytokines and the number of microglia and astrocytes. On the other hand, α-secretase has been involved in the shedding of certain cytokines, potentiating their activity. See text for further details of individual interactions. Numbers on the diagram correspond to the appropriate references in the review.