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.

中文翻译：

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一种抗淀粉样蛋白生成的疗法，专门阻断小鼠创伤事件的巩固

创伤后应激障碍（PTSD）是一种精神健康疾病，是由暴露于创伤事件引发的，该事件表现为痛苦，侵入性记忆和负面的情绪变化。到目前为止，除对症姑息治疗外，没有有效的PTSD治疗方法。基于功能性淀粉样蛋白胞质聚腺苷酸化元素结合蛋白3（CPEB3）在记忆整合中的意义，我们提出其活性淀粉样蛋白状态可通过阻止通过聚谷氨酰胺结合肽1（QBP1）创伤记忆的整合来作为可能的治疗靶点。 ，以前在果蝇中研究过的淀粉样蛋白低聚抑制剂。为了在哺乳动物中验证这一想法，我们在这里开发了一种组成型表达QBP1肽的转基因小鼠。我们首先评估了该肽对动物正常发育的无害性，该动物也表现出正常的运动活性和焦虑性。通过执行一系列的标准记忆范例，我们然后证明了QBP1小鼠的海马依赖性和厌恶性记忆受损。此外，有经验的小鼠海马中的蛋白表达表明QBP1小鼠不会增加其淀粉样蛋白的低聚水平，这表明处于非活性状态的CPEB3蛋白被阻断。QBP1阻断小鼠厌恶记忆的能力代表了预防和治疗急性应激和创伤后应激障碍的新型药理学方法的概念证明。