Journal
TOXINS
Volume 13, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/toxins13010033
Keywords
neurite outgrowth; scorpion toxin; potassium channel; nerve growth factor
Categories
Funding
- National Natural Science Foundation of China [81903826, 81972960, 21777192, 81473539]
- National Science and Technology Major Projects for Major New Drugs Innovation and Development [2018ZX09101003-004-002]
- China Postdoctoral Science Foundation [2018M630645, 2018M642371]
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The research identified a new scorpion toxin, BmK NSPK, which enhances neurite extension through increasing the release of nerve growth factor and TrkA signaling pathway. This provides a new theoretical basis for developing treatments for spinal cord neuron development and regeneration using K-v channels.
Scorpion toxins represent a variety of tools to explore molecular mechanisms and cellular signaling pathways of many biological functions. These toxins are also promising lead compounds for developing treatments for many neurological diseases. In the current study, we purified a new scorpion toxin designated as BmK NSPK (Buthus martensii Karsch neurite-stimulating peptide targeting K-v channels) from the BmK venom. The primary structure was determined using Edman degradation. BmK NSPK directly inhibited outward K+ current without affecting sodium channel activities, depolarized membrane, and increased spontaneous calcium oscillation in spinal cord neurons (SCNs) at low nanomolar concentrations. BmK NSPK produced a nonmonotonic increase on the neurite extension that peaked at similar to 10 nM. Mechanistic studies demonstrated that BmK NSPK increased the release of nerve growth factor (NGF). The tyrosine kinases A (TrkA) receptor inhibitor, GW 441756, eliminated the BmK NSPK-induced neurite outgrowth. BmK NSPK also increased phosphorylation levels of protein kinase B (Akt) that is the downstream regulator of TrkA receptors. These data demonstrate that BmK NSPK is a new voltage-gated potassium (K-v) channel inhibitor that augments neurite extension via NGF/TrkA signaling pathway. K-v channels may represent molecular targets to modulate SCN development and regeneration and to develop the treatments for spinal cord injury.
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