Systematic analysis reveals the action mechanisms and medicinal implications of latroeggtoxin-VI

Latrodectus spp. spiders, most often called black widow spiders, are one of the most venomous spiders known in the world. Different from many other venomous animals, Latrodectus spp. spiders have toxic components not only in their venom glands, but also in other parts of the adult spider body, newborn spiderlings and even the eggs. Latroeggtoxin-VI (LETX-VI), a bioactive peptide found from the eggs of spider Latrodectus tredecimguttatus, has been shown to extensively affect the metabolic processes in nerve cells via multiple action mechanisms. Due to its abilities to promote the synthesis, transport and release of dopamine, down-regulate the expression of α-synuclein, inhibit excessive inflammation, protect nerve cells, transmembrane deliver drugs, etc., LETX-VI is suggested to have application prospects in combating diabetes mellitus and central nervous system disorders such as Parkinson′s disease and depression. This review presents our understanding of the LETX-VI, including its properties, structure, action mechanisms, and potential applications. It should be pointed out that: i) almost all currently available data on LETX-VI have been generated by a single research group, and there are no independent replications; ii) no direct pharmacokinetic or quantitative blood-brain barrier penetration measurements, and no systematic in vivo dose-response studies; and iii) therefore, all therapeutic implications discussed in this review should be regarded as highly preliminary and hypothesis-generating rather than confirmatory.