Disulfide bonds location - Cys6-Cys26, Cys12-Cys31, Cys16-Cys33, Cys21-Cys36
The Vm24 toxin, also known as Vaejovis mexicanus peptide 24, is a potent blocker of Kv1.3 in human lymphocytes. Isolated from the venom of the Mexican scorpion Vaejovis mexicanus smithi, Vm24 is a 36-residue peptide with a molecular mass of 3864 Da, and has been identified as the first example of a new subfamily of α-type K(+) ion channel blockers (α-KTx 23.1)1.
Vm24, a natural immunosuppressive peptide, potently and selectively blocks Kv1.3 in human T cells with high affinity. The blockage of Kv1.3 channels in T cells is a promising therapeutic approach for the treatment of autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus2.
The voltage-gated potassium channel known as Kv1.3 (KCNA3) is expressed by a subset of chronically activated memory T cells and plays an important role in their activation and proliferation, especially in primary malignant T cells. The potent Kv1.3 inhibitor Vm24 inhibits CD3/CD28-induced proliferation and IL-9 expression, thus inhibiting activation-induced proliferation as well as cytokine and cytokine receptor expression in malignant T cells3.
Due to its high specificity, the Vm24 toxin enables to define the downstream functions of Kv1.3 channels in human CD4+ TEM lymphocytes. Blocking Kv1.3 channels profoundly affects the mRNA synthesis machinery, the unfolded protein response and intracellular vesicle transport, impairing the synthesis and secretion of cytokines in response to TCR engagement. This underscores the role of Kv1.3 channels in regulating TEM lymphocyte function4.
KV1.3 blockers change the course of Alzheimer's Disease (AD) development, reducing microglial cytotoxic activation and increasing neural stem cell differentiation. KV1.3 blockers inhibit microglia-mediated neurotoxicity in cell cultures, reducing the expression and production of the pro-inflammatory cytokines IL-1β and TNF-α via the NF-kB and p38MAPK pathway. Microglia activation correlates with an increase in KV1.3 channel expression and current density. Several studies highlight the importance of KV1.3 in the activation of the inflammatory response and the inhibition of neural progenitor cell proliferation and neuronal differentiation. Thus, KV1.3 blockers such as Vm24 possess potential therapeutic benefits for patients suffering from Alzheimer’s disease5