Apoptosis is a kind of programmed cell death that’s required in several physiological functions such as embryogenesis, cell turnover and response to pathogens. OMoreover, the BRAG1 mediated synaptic depression, which involves activation, is mediated by synaptic trafficking of GluA1 containing AMPA Rs. Together, these results suggest that BRAG1 Arf6 depresses synaptic transmission via regulating Rap2 JNK PP2B signaling. Our results suggest a novel synaptic signaling system whose dysregulation results in Xlinked mental retardation. HSP70 inhibitor Previous studies have examined the signaling and synaptic mechanisms for two other X linked mental disorders, oligophrenin 1 associated X linked mental retardation and fragile X . . Loss of function of oligophrenin 1 is thought to be responsible for the cognitive impairment related to X linked mental retardation, and recent evidence shows that oligophrenin 1 signals synaptic elimination of GluA2 containing AMPA Rs in a synaptic activity dependent manner. In whereas NMDA Kiminas dependent LTP is dramatically reduced in the knockout animals, FMR1 knockout mice, a mouse model for fragile X syndrome, mGluAdependent LTD is modestly up regulated by 10-15. The increased mGluA dependent LTD is mediated by increased Arc signaling, which handles p38 MAPK mediated synaptic removal of GluA2 containing AMPA Rs. High mGluR signaling seems Posttranslational modification (PTM) in charge of several syndromic features of vulnerable X, including the altered ocular dominance plasticity, seizure and passive avoidance. . The deficiency in LTP is due to the selective impairment of signal transduction between Ras and PI3K that abolishes synaptic supply of GluA1 containing AMPA Rs. This inferior LTP is responsible for the impaired active, advanced level associative learning linked with fragile X, which will be consistent with the finding that synaptic trafficking of GluA1 containing AMPA Rs is essential for experience dependent synaptic plasticity and associative learning. Here, we report that BRAG1 Arf6 regulates the JNKmediated synaptic elimination Erlotinib clinical trial of GluA1 containing AMPA Rs. . Furthermore, BRAG1 variations associated with nonsyndromic X linked mental retardation impair equally JNK signaling and synaptic trafficking of GluA1, however not GluA2 containing AMPA Rs. These results thus provide the initial evidence that dysregulation of JNK signaling and synaptic treatment of GluA1 containing AMPA Rs may also bring about X linked mental retardation, and provide a brand new mechanistic explanation for how mutations that either hinder or enhance Arf6 activity may all end in nonsyndromic X linked mental impairment. D the other hand aberrant apoptosis has been implicated in several neurodegenerative situations including Parkinsons disease, Huntingtons disease and Alzheimers disease as well as acute injuries such as stroke and spinal-cord injury. For that reason, understanding the upstream signaling pathways that control apoptosis in neurons is crucial for the development of treatments for these destructive neurological conditions.