Apoptosis is a complex cellular process involved in many steps of development and regulated by multiple pathways. Its activation is triggered mainly through two pathways: extrinsic (or death receptor) and intrinsic (or mitochondrial) pathways [113]. In addition, apoptosis is regulated by a number of intracellular signaling pathways, including MAPK signaling. In the CNS, MAPK signaling regulates the expression of transcription factors involved in learning, memory, cell proliferation, and apoptosis. This pathway responds to extracellular stimuli by phosphorylating c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38 and other kinases [117, 118]. Specifically, activation of p38 and JUK leads to inflammation and apoptosis, while ERK/MAPK signaling promotes cell growth and development, acting as anti-apoptotic signals. However, under some circumstances, ERK/MAPK can function in a pro-apoptotic manner [119]. For example, a previous study reported that inhibition of ERK expression protected neurons from low potassium conditions, while constitutive overexpression of ERK promoted cell death, suggesting an effect on neurodegeneration [120]. In our data, the expression of multiple components in all three of these pathways was significantly increased in SZ neurons, implying combinational effects towards apoptosis.
