journal article·2025-09Open access

Activation of Kir4.1 Channels by 2‐D08 Promotes Myelin Repair in Multiple Sclerosis

Mingdong Liu, Shengyu Jin, Xin Fu, Chong Xie, Yi Chen, Liangtang Chang, Yongheng Fan, Donghua He, Xiaoqi Hong, Xi Shen, Xiaoli Zheng, Qiyue Wang, Dao Shi, Fangyuan Li, Daishun Ling, Yangtai Guan, Neng Gong, Xiaoping Tong

Advanced Science· Volume 12· Issue 34

Abstract

Abstract Multiple sclerosis (MS) is a chronic inflammatory disease that leads to myelin loss and neurological dysfunction. Clinical studies show increased anti‐Kir4.1 antibody levels in MS patients' serum, indicating its diagnostic potential. However, the specific mechanism has remained elusive. In a mouse model of experimental autoimmune encephalomyelitis (EAE), it is found that impaired Kir4.1 channels in oligodendrocyte precursor cells (OPCs) hindered myelin repair in the spinal cord. Using a thermal shift assay (TSA), the small molecule 2‐D08 is identified, which effectively activated Kir4.1 channels and reduced demyelination in both EAE mice and marmosets. The neuroprotective effects are mainly due to enhanced phosphorylation of FYN tyrosine kinase, promoting OPCs differentiation. The findings highlight the critical role of Kir4.1 channels in MS pathogenesis and suggest that pharmacological activation of these channels by 2‐D08 can be a promising therapeutic strategy for enhancing brain recovery in demyelinating diseases.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Multiple Sclerosis Research Studies · Neurogenesis and neuroplasticity mechanisms · Neuroinflammation and Neurodegeneration Mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Obstetrics and Gynecology Songjiang Research Institute Shanghai Key Laboratory of Emotions and Affective Disorders Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 201600 China

Department of Anatomy and Physiology Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

Center for Brain Science Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine Shanghai 200127 China

Department of Neurology Ren Ji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200127 China

Institute of Neuroscience Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences Shanghai 200031 China

Frontiers Science Center for Transformative Molecules School of Chemistry and Chemical Engineering School of Biomedical Engineering National Center for Translational Medicine Shanghai Jiao Tong University Shanghai 200240 China

Songjiang Research Institute Shanghai Key Laboratory of Emotions and Affective Disorders Shanghai Jiao Tong University School of Medicine Shanghai 201600 China

Department of Neurology, Punan Branch of Renji Hospital Shanghai Jiaotong University School of Medicine Shanghai 200125 China

Funding

National Natural Science Foundation of China

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