Activation of Anti-Survival Pathways

Two pathways lead to apoptosis in mature neurons the intrinsic mitochondria-dependent pathway and the death receptor-induced extrinsic (mitochondria-independent) pathway. These pathways seldom function exclusively and often converge with each other. 

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) represent tw o enzyme classes that, respectively, catalyze forward and backward reaction kinetics of lysine residue acetylation of nucleosomal histones and various transcription 

HDACs attain facilitated gain-of-funcdon, thereby unsetding the acetyladon homeostasis. At this stage, dranscripdon of pro-survival genes is profoundly repressed due to collapsed histone gates at their promoter regions. Furthermore, several dranscripdon factors like CREB, NF-kB, Spl, and HIF fail to perform their pro-survival dranscripdon dudes as all these TFs require to be acetylated for acdvadon. 

---