Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
Department of Biomedical Sciences and Medicine, Center for Biomedical Research (CBMR), University of Algarve, Faro, Portugal.
Trends Endocrinol Metab. 2017 Apr;28(4):309-318. doi: 10.1016/j.tem.2016.12.006. Epub 2017 Jan 21.
Ataxin-2 is a polyglutamine protein implicated in several biological processes such as RNA metabolism and cytoskeleton reorganization. Ataxin-2 is highly expressed in various tissues including the hypothalamus, a brain region that controls food intake and energy balance. Ataxin-2 expression is influenced by nutritional status. Emerging studies discussed here now show that ataxin-2 deficiency correlates with insulin resistance and dyslipidemia, an action mediated via the mTOR pathway, suggesting that ataxin-2 might play key roles in metabolic homeostasis including body weight regulation, insulin sensitivity, and cellular stress responses. In this review we also discuss the relevance of ataxin-2 in the hypothalamic regulation of energy balance, and its potential as a therapeutic target in metabolic disorders such as obesity.
Ataxin-2 是一种多聚谷氨酰胺蛋白,涉及多种生物学过程,如 RNA 代谢和细胞骨架重组。Ataxin-2 在多种组织中高度表达,包括下丘脑,这是控制食物摄入和能量平衡的大脑区域。Ataxin-2 的表达受营养状况的影响。目前讨论的新出现的研究表明,ataxin-2 缺乏与胰岛素抵抗和血脂异常相关,这种作用是通过 mTOR 途径介导的,表明 ataxin-2 可能在代谢稳态中发挥关键作用,包括体重调节、胰岛素敏感性和细胞应激反应。在这篇综述中,我们还讨论了 ataxin-2 在能量平衡的下丘脑调节中的相关性,以及它作为肥胖等代谢紊乱的治疗靶点的潜力。