The ChIP-Seq procedure allows to map TF-target sequences and provide a functional readout of gene activation in complex tissues, such as the brain, and under different experimental conditions: i.e., environmental enrichment, aging, neurodegeneration, neuroinflammation, etc. Understanding the downstream targets of signaling pathways critical for plasticity and neurodegeneration will facilitate the discrimination of beneficial versus detrimental genes’ products that can be employed for developing therapeutic strategies targeting brain diseases. This evidence concerns the gene TF and brain disorder.