Mitochondrial-derived DAMPs (including mtDNA, formyl peptides, RNA, ATP, certain mitochondrial-localized proteins, and cardiolipin) activate pattern recognition receptors (PRRs) such as toll-like receptors, formyl peptide receptors, or the NLRP3 inflammasome. Activation of these receptors leads to downstream phosphorylation and activation of p38 MAPK. Activated p38 MAPK can then activate NFκB, inducing its translocation to the nucleus. NFκB facilitates the transcription of cytokines such as TNFα. TNFα can further amplify an inflammatory cascade by independently activating p38 MAPK and NFκB signaling. NFκB may also initiate APP transcription.