School of Life Sciences, Gwangju Institute Science and Technology (GIST), Gwangju, Republic of Korea.
Department of Biomedical Science and Engineering, GIST, Gwangju, Republic of Korea.
Commun Biol. 2024 Sep 30;7(1):1218. doi: 10.1038/s42003-024-06879-y.
Energy homeostasis and sleep have a bidirectional relationship. Cereblon (CRBN) regulates energy levels by ubiquitinating the AMP-activated protein kinase(AMPK), an energy sensor. However, whether CRBN participates in sleep is unclear. Here, we examine sleep-wake patterns in Crbn and Crbn mice during 24-h baseline, 6-h sleep deprivation (SD), and following 6-h recovery sleep (RS). At baseline, overall sleep patterns are similar between genotypes. However, SD decreases CRBN expression in Crbn mice and increases phospho-Tau, phospho-α-synuclein, DNAJA1 (DJ2), and DNAJB1 (DJ1) in both genotypes, with Crbn mice showing a lesser extent of increase in p-Tau and p-α-synuclein and a higher level of heat shock protein 70 (HSP70), DJ2, and DJ1. During RS, Crbn mice show increased slow-wave activity in the low-delta range (0.5-2.5 Hz), suggesting higher homeostatic sleep propensity associated with AMPK hyperactivation. By illuminating the role of CRBN in regulating sleep-wake behaviors through AMPK, we suggest CRBN as a potential therapeutic target for managing sleep disorders and preventing neurodegeneration.
能量平衡和睡眠之间存在双向关系。cereblon (CRBN) 通过泛素化 AMP 激活蛋白激酶 (AMPK) 来调节能量水平，AMPK 是一种能量传感器。然而，CRBN 是否参与睡眠尚不清楚。在这里，我们研究了 Crbn 和 Crbn 小鼠在 24 小时基线、6 小时睡眠剥夺 (SD) 和随后的 6 小时恢复睡眠 (RS) 期间的睡眠-觉醒模式。在基线时，两种基因型的整体睡眠模式相似。然而，SD 会降低 Crbn 小鼠中的 CRBN 表达，并增加两种基因型中的磷酸化 Tau、磷酸化 α-突触核蛋白、DNAJA1 (DJ2) 和 DNAJB1 (DJ1)，Crbn 小鼠中的磷酸化 Tau 和磷酸化 α-突触核蛋白增加程度较小，热休克蛋白 70 (HSP70)、DJ2 和 DJ1 水平较高。在 RS 期间，Crbn 小鼠在低 delta 范围内 (0.5-2.5 Hz) 显示出增加的慢波活动，表明与 AMPK 过度激活相关的更高的稳态睡眠倾向。通过阐明 CRBN 通过 AMPK 调节睡眠-觉醒行为的作用，我们认为 CRBN 是管理睡眠障碍和预防神经退行性变的潜在治疗靶点。
