PENK and Alzheimer disease: Interestingly, TNF, whose transcription was not altered upon knockdown of Arc, regulates 15 genes (Figure 17), the top five of which are Casp8 (neuroinflammation) [368], Ptgs2 (also regulated by APP and CREB1), Gabrg2 (neuroinflammation) [369,370], Bdnf (synaptogenesis, neuroinflammation, AD progression) [371,372,373,374] and Penk (opioid signalling, AD progression) [375].