FAIM blocking peptide

The long isoform of Fas apoptosis inhibitory molecule (FAIM-L) is a neuron-specific death receptor antagonist that modulates apoptotic cell death and mechanisms of neuronal plasticity. FAIM-L exerts its antiapoptotic action by binding to X-linked inhibitor of apoptosis protein (XIAP), an inhibitor of caspases, which are the main effectors of apoptosis. XIAP levels are regulated by the ubiquitin-proteasome pathway. FAIM-L interaction with XIAP prevents the ubiquitination and degradation of the latter, thereby allowing it to inhibit caspase activation. This interaction also modulates non-apoptotic functions of caspases, such as the endocytosis of AMPA receptor (AMPAR) in hippocampal long-term depression (LTD). The molecular mechanism of action exerted by FAIM-L is unclear since the consensus binding motifs are still unknown. Here, we performed a two-hybrid screening to discover novel FAIM-L-interacting proteins. We found a functional interaction of SIVA-1 with FAIM-L. SIVA-1 is a proapoptotic protein that has the capacity to interact with XIAP. We describe how SIVA-1 regulates FAIM-L function by disrupting the interaction of FAIM-L with XIAP, thereby promoting XIAP ubiquitination, caspase-3 activation and neuronal death. Furthermore, we report that SIVA-1 plays a role in receptor internalization in synapses. SIVA-1 is upregulated upon chemical LTD induction, and it modulates AMPAR internalization via non-apoptotic activation of caspases. In summary, our findings uncover SIVA-1 as new functional partner of FAIM-L and demonstrate its role as a regulator of caspase activity in synaptic function.

BackgroundFood allergy is often a life-long condition that requires constant vigilance to prevent accidental exposure and avoid potentially life-threatening symptoms. Parents' confidence in managing their child's food allergy may relate to the poor quality of life anxiety and worry reported by parents of food-allergic children. ObjectiveThe aim of this study was to develop and validate the first scale to measure parental confidence (self-efficacy) in managing food allergy in their child. MethodsThe Food Allergy Self-Efficacy Scale for Parents (FASE-P) was developed through interviews with 53 parents, consultation of the literature and experts in the area. The FASE-P was then completed by 434 parents of food-allergic children from a general population sample in addition to the General Self-Efficacy Scale (GSES), the Food Allergy Quality of Life Parental Burden Scale (FAQL-PB), the General Health Questionnaire-12 (GHQ-12) and the Food Allergy Impact Measure (FAIM). A total of 250 parents completed the retest of the FASE-P. ResultsFactor and reliability analysis resulted in a 21-item scale with five subscales. The overall scale and subscales have good to excellent internal consistency (Cronbach's of 0.63-0.89), and the scale is stable over time. There were low to moderate significant correlations with the GSES, FAIM and GHQ-12 and strong correlations with the FAQL-PB, with better parental confidence relating to better general self-efficacy, better quality of life and better mental health in the parent. Poorer self-efficacy was related to egg and milk allergy; self-efficacy was not related to severity of allergy. Conclusions and clinical relevanceThe FASE-P is a reliable and valid scale for use with parents from a general population. Its application within clinical settings could aid provision of advice and improve targeted interventions by identifying areas where parents have less confidence in managing their child's food allergy.