Massaly Nicolas, Francès Bernard, Moulédous Lionel
Centre de Recherches sur la Cognition Animale, Centre National de la Recherche Scientifique UMR 5169 Toulouse, France ; Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique UMR 5089 Toulouse, France ; Université Paul Sabatier Toulouse III Toulouse, France.
Centre de Recherches sur la Cognition Animale, Centre National de la Recherche Scientifique UMR 5169 Toulouse, France ; Université Paul Sabatier Toulouse III Toulouse, France.
Front Mol Neurosci. 2015 Jan 6;7:99. doi: 10.3389/fnmol.2014.00099. eCollection 2014.
Because of its ability to regulate the abundance of selected proteins the ubiquitin proteasome system (UPS) plays an important role in neuronal and synaptic plasticity. As a result various stages of learning and memory depend on UPS activity. Drug addiction, another phenomenon that relies on neuroplasticity, shares molecular substrates with memory processes. However, the necessity of proteasome-dependent protein degradation for the development of addiction has been poorly studied. Here we first review evidences from the literature that drugs of abuse regulate the expression and activity of the UPS system in the brain. We then provide a list of proteins which have been shown to be targeted to the proteasome following drug treatment and could thus be involved in neuronal adaptations underlying behaviors associated with drug use and abuse. Finally we describe the few studies that addressed the need for UPS-dependent protein degradation in animal models of addiction-related behaviors.
由于泛素蛋白酶体系统（UPS）具有调节特定蛋白质丰度的能力，它在神经元和突触可塑性中发挥着重要作用。因此，学习和记忆的各个阶段都依赖于UPS的活性。药物成瘾是另一种依赖神经可塑性的现象，它与记忆过程共享分子底物。然而，蛋白酶体依赖性蛋白质降解在成瘾发展中的必要性尚未得到充分研究。在这里，我们首先回顾文献中的证据，即滥用药物会调节大脑中UPS系统的表达和活性。然后，我们列出了一系列蛋白质，这些蛋白质在药物治疗后已被证明是蛋白酶体的作用靶点，因此可能参与了与药物使用和滥用相关行为的神经元适应性变化。最后，我们描述了少数针对成瘾相关行为动物模型中UPS依赖性蛋白质降解需求的研究。
