No. 18

Time：2:00 PM, March 22, 2024 (Friday)

Location: Room 1322, North Tower, Basic Research Building, Capital Medical University

Host: Lin Mei

          Chinese Institutes for Medical Research, Beijing

Speaker: Xiaoping Tong 

          Investigator

          Shanghai Jiao Tong University School of Medicine

Title: New strategy of targeting Kir4.1 channels in the repair of multiple sclerosis

Abstract:

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Axonal demyelination is considered to be the main factor leading to permanent neurological dysfunction in MS patients. Up to now, many believe autoimmune pathogenesis plays a key role in MS, but its target remains elusive. Here, we found that impaired Kir4.1 channels in spinal cord initially occurred in NG2 glia but not astrocytes in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Through thermal shift assay screening, we identified a small molecular compound HT001 to be an activator of Kir4.1 channel. Treating EAE mice with HT001, we found that this molecule protected EAE-induced demyelination in spinal cord and ultimately improved motor functions in a series of behavioral tests of EAE mice. Our finding highlights a key role of Kir4.1 channel in MS pathogenesis and pharmacological activation of Kir4.1 channel by HT001 illustrates a potential neuroprotective strategy for functional brain recovery in demyelinating diseases.

Selected publications:

Hong X, Jian Y, Ding S, Zhou J, Zheng X, Zhang H, Zhou B, Zhuang C, Wan, J*, Tong X*. Kir4.1 channel activation in NG2 glia contributes to remyelination in ischemic stroke. EBioMedicine. 2023, 87, 104406.

Zhang X, Liu Y, Hong X, Li X, Meshul CK, Moore C, Yang Y, Han Y, Li W, Xin Q, Lou H, Duan S, Xu T, Tong X*. NG2 glia-derived GABA release tunes inhibitory synapses and contributes to stress-induced anxiety. Nature Communications. 2021, 12(1): 5740.

Zhou B, Zhu Z, Ransom BR*, Tong X*. Oligodendrocyte lineage cells and depression. Molecular Psychiatry. 2021, 26(1): 103~117.