Apoptosis is a kind of programmed cell death that’s needed in several physiological processes such as cell turnover, embryogenesis and response to pathogens. OMoreover, the BRAG1 mediated synaptic depression, which involves Arf6 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 device whose dysregulation results in Xlinked mental retardation. supplier Dasatinib Previous studies have examined the signaling and synaptic mechanisms for two other X linked mental problems, oligophrenin 1 associated X linked mental retardation and fragile X syndrome. . Loss of function of oligophrenin 1 is thought to be responsible for the cognitive impairment related to X associated mental retardation, and recent evidence suggests that oligophrenin 1 signals synaptic removal of GluA2 containing AMPA Rs in a synaptic activity dependent manner. In FMR1 knockout mice, a mouse model for fragile X syndrome, mGluAdependent LTD is modestly up regulated by 10-15, whereas NMDA Page1=46 dependent LTP is considerably reduced in the knockout animals. The increased mGluA dependent LTD is mediated by increased Arc signaling, which controls p38 MAPK mediated synaptic removal of GluA2 containing AMPA Rs. Exaggerated mGluR signaling seems Infectious causes of cancer accountable for several syndromic top features of vulnerable X, like the altered ocular dominance plasticity, seizure and passive avoidance. . The flaw in LTP is because of the selective impairment of signal transduction between Ras and PI3K that abolishes synaptic delivery of GluA1 containing AMPA Rs. This poor LTP is liable for the impaired active, advanced level associative learning linked with fragile X, which can be consistent with the finding that synaptic trafficking of GluA1 containing AMPA Rs is important for knowledge dependent synaptic plasticity and associative learning. Here, we report that BRAG1 Arf6 regulates the JNKmediated synaptic elimination price Dabrafenib of GluA1 containing AMPA Rs. . Furthermore, BRAG1 mutations associated with nonsyndromic X linked mental retardation damage equally JNK signaling and synaptic trafficking of GluA1, although not GluA2 containing AMPA Rs. These results ergo provide the first proof that dysregulation of JNK signaling and synaptic removal of GluA1 containing AMPA Rs may also lead to X linked mental retardation, and provide a new mechanistic explanation for how mutations that either hinder or enhance Arf6 activity may all bring about nonsyndromic X linked mental disability. n the other hand aberrant apoptosis is implicated in a number of neurodegenerative situations including Parkinsons disease, Huntingtons disease and Alzheimers disease in addition to acute injuries such as stroke and back injury. Consequently, knowing the upstream signaling pathways that control apoptosis in neurons is a must for the development of solutions for these harmful neurological problems.