Chimeric protein 2 (CHN2) regulating Rac GTPase activity is the receptor for diglyceride and phorbol ester.[9] Rac GTPase is a member of the Rho-GTPase family that exert important influences on the development of neural networks and the formation of neurites and growth cones. Rac plays an important role in the regulation of actin skeletal structure, migration, metabolism, transformation, gene expression, and cell cycle progression.[9] We hypothesized that long-term abuse of MA would induce the abnormal methylation of CHN2 gene, change the expression of chimeric protein 2, and affect the activity of Rac signaling system. This mechanism resulted in the remodeling of the actin cytoskeleton and the adaptive changes in neurons, which eventually led to the formation of addictive behavior.[16] In addition, abnormal methylation of the CHN2 gene could also lead to addiction behavior by affecting JNK signaling pathway. JNK signaling pathway in the hippocampus is involved in learning and memory mechanism and is related to addictive behavior.[17, 18] In addition, it has been reported that chimeric protein 2 might be involved in the regulation of JNK signaling in the hippocampal neurons.[19]
