Kv1.3 Channel as a Key Therapeutic Target for Neuroinflammatory Diseases: State of the Art and Beyond

• Published in: Frontiers in neuroscience 2020-01, Vol.13, p.1393-1393
• Main Authors: Wang, Xiaoli, Li, Guoyi, Guo, Jingkang, Zhang, Zhiping, Zhang, Shuzhang, Zhu, Yudan, Cheng, Jiwei, Yu, Lu, Ji, Yonghua, Tao, Jie
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amino acids; Autoimmune diseases; Chemical bonds; Clinical trials; Diabetes; Epilepsy; Inflammation; Kv1.3; Lymphocytes; Lymphocytes T; Microglial cells; Movement disorders; Multiple sclerosis; Neurodegenerative diseases; neuroinflammatory disease; Neuroscience; Parkinson's disease; Polypeptides; Potassium; Potassium channels (voltage-gated); Psoriasis; Rheumatoid arthritis; ShK; stroke; Therapeutic applications; Toxins
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2019.01393

It remains a challenge for the effective treatment of neuroinflammatory disease, including multiple sclerosis (MS), stroke, epilepsy, and Alzheimer's and Parkinson's disease. The voltage-gated potassium Kv1.3 channel is of interest, which is considered as a novel therapeutic target for treating neuroinflammatory disorders due to its crucial role in subsets of T lymphocytes as well as microglial cells. Toxic animals, such as sea anemones, scorpions, spiders, snakes, and cone snails, can produce a variety of toxins that act on the Kv1.3 channel. The K channel blocking toxin (ShK) from the sea anemone is proved as a classical blocker of Kv1.3. One of the synthetic analogs ShK-186, being developed as a therapeutic for autoimmune diseases, has successfully completed first-in-man Phase 1 trials. In addition to addressing the recent progress on the studies underlying the pharmacological characterizations of ShK on MS, the review will also explore the possibility for clinical treatment of ShK-like Kv1.3 blocking polypeptides on other neuroinflammatory diseases.