Groen Ewout J N, Gillingwater Thomas H
Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK; Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, UK; Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
Trends Mol Med. 2015 Oct;21(10):622-632. doi: 10.1016/j.molmed.2015.08.003.
Neurodegenerative diseases are a leading cause of disability and early death. A common feature of these conditions is disruption of protein homeostasis. Ubiquitin-like modifier activating enzyme 1 (UBA1), the E1 ubiquitin-activating enzyme, sits at the apex of the ubiquitin cascade and represents an important regulator of cellular protein homeostasis. Critical contributions of UBA1-dependent pathways to the regulation of homeostasis and degeneration in the nervous system are emerging, including specific disruption of UBA1 in spinal muscular atrophy (SMA) and Huntington's disease (HD). In this review we discuss recent findings that put UBA1 at the centre of cellular homeostasis and neurodegeneration, highlighting the potential for UBA1 to act as a promising therapeutic target for a range of neurodegenerative diseases.
神经退行性疾病是导致残疾和过早死亡的主要原因。这些病症的一个共同特征是蛋白质稳态的破坏。泛素样修饰激活酶1（UBA1），即E1泛素激活酶，位于泛素级联反应的顶端，是细胞蛋白质稳态的重要调节因子。依赖UBA1的途径对神经系统稳态调节和神经变性的关键作用正在显现，包括脊髓性肌萎缩症（SMA）和亨廷顿舞蹈症（HD）中UBA1的特异性破坏。在本综述中，我们讨论了最近的研究发现，这些发现将UBA1置于细胞稳态和神经变性的中心位置，强调了UBA1作为一系列神经退行性疾病潜在治疗靶点的可能性。
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