TY - JOUR T1 - An anti-amyloidogenic treatment to specifically block the consolidation of traumatic events in mouse JF - bioRxiv DO - 10.1101/2020.01.21.913053 SP - 2020.01.21.913053 AU - Paula López-García AU - Daniel Ramírez de Mingo AU - Kerry R. McGreevy AU - Anna Pallé AU - Helena Akiko Popiel AU - Andrea Santi AU - Yoshitaka Nagai AU - José Luís Trejo AU - Mariano Carrión-Vázquez Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/19/2020.01.21.913053.abstract N2 - Post-traumatic stress disorder (PTSD) is a mental health disorder triggered by the exposure to a traumatic event that manifests with anguish, intrusive memories and negative mood changes. So far, there is no efficient treatment for PTSD other than symptomatic palliative care. Based on the implication of the functional amyloid cytoplasmic polyadenylation element binding protein-3 (CPEB3) in the consolidation of memory, we propose its active amyloid state as a possible therapeutic target by blocking the consolidation of traumatic memories through polyglutamine binding peptide 1 (QBP1), an inhibitor of the amyloid oligomerization previously investigated in Drosophila.To test this idea in mammals, here we have developed a transgenic mouse that constitutively expresses QBP1 peptide. We first assessed the innocuousness of this peptide for the normal development of the animal, which also showed normal locomotor activity and anxiety. By performing a battery of standard memory paradigms, we then showed that hippocampal-dependent and aversive memories were impaired in the QBP1 mice. Furthermore, protein expression in the hippocampi of experienced mice showed that QBP1 mice do not increase their levels of amyloid oligomerization, evincing the blockade of the CPEB3 protein in its inactive state. The ability of QBP1 to block aversive memories in mice represents the proof of concept of a novel pharmacological approach for prophylaxis and therapy of acute stress and post-traumatic stress disorders.Competing Interest StatementMC.-V. is co-inventor of a patent on QBP1 as a lead compound for PTSD and ASD (PCT/EP2016/057801) and has received funding from the Spanish Ministry of Economy (SAF2013-49179-C2-1-R and SAF2016-76678-C2-1-R). The rest of the authors of this publication reported no biomedical financial interests or potential conflicts of interest. ER -