Unraveling neuroprotection with Kv1.3 potassium channel blockade by a scorpion venom peptide

Sci Rep. 2024 Nov 13;14(1):27888. doi: 10.1038/s41598-024-79152-1.

Abstract

Voltage-gated potassium channels play a crucial role in cellular repolarization and are potential therapeutic targets in neuroinflammatory disorders and neurodegenerative diseases. This study explores Tityus bahiensis scorpion venom for neuroactive peptides. We identified the αKtx12 peptide as a potent neuroprotective agent. In SH-SY5Y cells, αKtx12 significantly enhances viability, validating its pharmacological potential. And in the animal model, we elucidate central nervous system (CNS) mechanism of αKtx12 through neuroproteomic analyses highlighting αKtx12 as a valuable tool for characterizing neuroplasticity and neurotropism, revealing its ability to elicit more physiological responses. The peptide's potential to promote cell proliferation and neuroprotection suggests a role in functional recovery from nervous system injury or disease. This research unveils the neuroactive potential of scorpion venom-derived αKtx12's, offering insights into its pharmacological utility. The peptide's impact on neuronal processes suggests a promising avenue for therapeutic development, particularly in neurodegenerative conditions.

Keywords: Hippocampus; Kv1.3; Neurotoxin; Peptide; Scorpion toxin; Voltage-gated potassium channel; αKtx12.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Humans
  • Kv1.3 Potassium Channel* / antagonists & inhibitors
  • Kv1.3 Potassium Channel* / metabolism
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotection / drug effects
  • Neuroprotective Agents* / pharmacology
  • Peptides / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Rats
  • Scorpion Venoms* / chemistry
  • Scorpion Venoms* / pharmacology

Substances

  • Scorpion Venoms
  • Kv1.3 Potassium Channel
  • Neuroprotective Agents
  • Peptides
  • Potassium Channel Blockers