Center for Brain Disorders Research, Capital Medical University, 10 Xi tou tiao, You an men, Feng tai District, 100069, Beijing, China.
Beijing Institute for Brain Disorders, 10 Xi tou tiao. You an men, Feng tai District, 100069, Beijing, China.
Cell Death Dis. 2018 Oct 17;9(11):1058. doi: 10.1038/s41419-018-1076-x.
The proprotein convertase Furin plays crucial roles in the pathology of many diseases. However, the specific role of furin in epilepsy remains unclear. In our study, furin protein was increased in the temporal neocortex of epileptic patients and in the hippocampus and cortex of epileptic mice. The furin transgenic (TG) mice showed increased susceptibility to epilepsy and heightened epileptic activity compared with wild-type (WT) mice. Conversely, lentivirus-mediated knockdown of furin restrained epileptic activity. Using whole-cell patch clamp, furin knockdown and overexpression influenced neuronal inhibitory by regulating postsynaptic gamma-aminobutyric acid A receptor (GABAR)-mediated synaptic transmission. Importantly, furin influenced the expression of GABAR β2/3 membrane and total protein in epileptic mice by changing transcription level of GABAR β2/3, not the protein degradation. These results reveal that furin may regulate GABAR-mediated inhibitory synaptic transmission by altering the transcription of GABAR β2/3 subunits in epilepsy; this finding could provide new insight into epilepsy prevention and treatment.
蛋白原转化酶 Furin 在许多疾病的病理学中起着至关重要的作用。然而，Furin 在癫痫中的具体作用尚不清楚。在我们的研究中，癫痫患者的颞叶皮质和癫痫小鼠的海马和皮质中 Furin 蛋白增加。与野生型（WT）小鼠相比，Furin 转基因（TG）小鼠对癫痫的易感性增加，癫痫活动加剧。相反，慢病毒介导的 Furin 敲低抑制了癫痫活动。通过全细胞膜片钳技术，Furin 的敲低和过表达通过调节突触后γ-氨基丁酸 A 受体（GABAR）介导的突触传递来影响神经元抑制。重要的是，Furin 通过改变 GABARβ2/3 亚基的转录水平而不是蛋白降解，影响癫痫小鼠中 GABARβ2/3 膜和总蛋白的表达。这些结果表明，Furin 可能通过改变 GABARβ2/3 亚基的转录来调节癫痫中的 GABAR 介导的抑制性突触传递；这一发现为癫痫的预防和治疗提供了新的思路。
