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Cell Death Dis. 2018 Oct 17;9(11):1058. doi: 10.1038/s41419-018-1076-x.

Transgenic overexpression of furin increases epileptic susceptibility.

Author information

1
Center for Brain Disorders Research, Capital Medical University, 10 Xi tou tiao, You an men, Feng tai District, 100069, Beijing, China.
2
Beijing Institute for Brain Disorders, 10 Xi tou tiao. You an men, Feng tai District, 100069, Beijing, China.
3
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, 400016, Chongqing, China.
4
Beijing Institute for Brain Disorders, 10 Xi tou tiao. You an men, Feng tai District, 100069, Beijing, China. xfyp@163.com.
5
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, 400016, Chongqing, China. xfyp@163.com.

Abstract

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 (GABAAR)-mediated synaptic transmission. Importantly, furin influenced the expression of GABAAR β2/3 membrane and total protein in epileptic mice by changing transcription level of GABAAR β2/3, not the protein degradation. These results reveal that furin may regulate GABAAR-mediated inhibitory synaptic transmission by altering the transcription of GABAAR β2/3 subunits in epilepsy; this finding could provide new insight into epilepsy prevention and treatment.

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