Ubiquitin-activating enzyme E1, UBA1, functions at the apex of the enzymatic ubiquitylation cascade, catalysing ubiquitin activation. UBA1 is thus of fundamental importance to the modulation of ubiquitin homeostasis and to all downstream ubiquitylation-dependent cellular processes, including proteolysis through the ubiquitin-proteasome system and selective autophagy. The proteasome-dependent and -independent functions of UBA1 contribute significantly to a range of processes crucial to neuronal health. The significance of UBA1 activity to neuronal health is clear in light of accumulating evidence implicating impaired UBA1 activity in a range of neurodegenerative conditions, including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and spinal muscular atrophy. Moreover, ubiquitylation-independent functions of UBA1 of importance to neuronal functioning have been proposed. Here, we summarise findings supporting the significant role of UBA1 in regulating neuronal functioning, and discuss the detrimental consequences of UBA1 impairment that contribute to neuronal dysfunction and degeneration.

泛素激活酶E1，UBA1在酶促泛素化级联的顶点起作用，催化泛素激活。因此，UBA1对于调节遍在蛋白稳态和所有下游遍在蛋白化依赖性细胞过程（包括通过遍在蛋白-蛋白酶体系统进行蛋白水解和选择性自噬）至关重要。UBA1的蛋白酶体依赖性和非依赖性功能对一系列对神经元健康至关重要的过程做出了重要贡献。根据越来越多的证据表明，在一系列神经退行性疾病（包括帕金森氏病，阿尔茨海默氏病，亨廷顿氏病和脊髓性肌萎缩症）中，UBA1活性受损的证据表明，UBA1活性对神经元健康具有重要意义。此外，已经提出了对神经元功能重要的UBA1的泛素化无关功能。在这里，我们总结了支持UBA1在调节神经元功能中的重要作用的发现，并讨论了UBA1损伤的有害后果，该损伤导致神经元功能障碍和变性。