Anderson Dina B, Zanella Camila A, Henley Jeremy M, Cimarosti Helena
Ipsen Bioinnovation Ltd, Units 4-10 The Quadrant, Barton Lane, Abingdon, OX14 3YS, UK.
Department of Pharmacology, Federal University of Santa Catarina, Campus Universitario - Trindade, Florianopolis, CEP, 88040-900, Brazil.
Adv Exp Med Biol. 2017;963:261-281. doi: 10.1007/978-3-319-50044-7_16.
The covalent posttranslational modifications of proteins are critical events in signaling cascades that enable cells to efficiently, rapidly and reversibly respond to extracellular stimuli. This is especially important in the CNS where the processes affecting synaptic communication between neurons are highly complex and very tightly regulated. Sumoylation regulates the function and fate of a diverse array of proteins and participates in the complex cell signaling pathways required for cell survival. One of the most complex signaling pathways is synaptic transmission.Correct synaptic function is critical to the working of the brain and its alteration through synaptic plasticity mediates learning, mental disorders and stroke. The investigation of neuronal sumoylation is a new and exciting field and the functional and pathophysiological implications are far-reaching. Sumoylation has already been implicated in a diverse array of neurological disorders. Here we provide an overview of current literature highlighting recent insights into the role of sumoylation in neurodegeneration. In addition we present a brief assessment of drug discovery in the analogous ubiquitin system and extrapolate on the potential for development of novel therapies that might target SUMO-associated mechanisms of neurodegenerative disease.
蛋白质的共价翻译后修饰是信号级联反应中的关键事件，使细胞能够高效、快速且可逆地响应细胞外刺激。这在中枢神经系统中尤为重要，因为影响神经元之间突触通讯的过程高度复杂且受到严格调控。SUMO化修饰调节多种蛋白质的功能和命运，并参与细胞存活所需的复杂细胞信号通路。最复杂的信号通路之一是突触传递。正确的突触功能对大脑的运作至关重要，其通过突触可塑性的改变介导学习、精神障碍和中风。对神经元SUMO化修饰的研究是一个新的、令人兴奋的领域，其功能和病理生理学意义深远。SUMO化修饰已经与多种神经疾病有关。在此，我们概述当前的文献，突出对SUMO化修饰在神经退行性变中作用的最新见解。此外，我们简要评估了类似泛素系统中的药物发现，并推断可能针对神经退行性疾病中与SUMO相关机制的新型疗法的开发潜力。
