Neurotoxic snake venoms in Mexico: Diversity and recent advances

Despite Mexico's unique diversity of venomous snakes, the neurotoxic components of their venoms have remained understudied. Fifteen years ago, no formal records existed of neurotoxic viper species in the country, and while Mexican elapids were presumed to be neurotoxic based on studies on the related species from other regions, their venoms had not been biochemically or functionally characterized. This review provides a comprehensive and updated synthesis of the current knowledge on neurotoxic venomous snake species in Mexico, with a focus on crotoxin-like phospholipases A₂ (PLA₂) in vipers and three-finger toxins (3FTx) and β-neurotoxic PLA₂s in elapids. Consistent crotoxin expression has now been documented in several rattlesnake species (e.g., Crotalus simus, C. tigrisandC. basiliscus), while others exhibit polymorphic expression or post-transcriptional regulation. Crotoxin-like neurotoxins have also been described in other viperid genera such as Mixcoatlus, Cerrophidion, and Ophryacus. In some Micrurus species, in addition to three-finger toxins, i.e. as α-neurotoxins, and neurotoxic phospholipases A₂, other toxin complexes have been identified whose functional synergy can result in high toxicity, even when each component alone may be non-lethal. This phenomenon has only been reported in particular species. While existing antivenoms in Mexico effectively neutralize venoms from Crotalus species that contain crotoxin-like components, higher doses may be required for genera whose venoms are poorly represented in the immunizing mixtures currently used for antivenom production. This review aims to summarize the current state of knowledge, and highlights the urgent need for continued research using omics approaches to better understand the evolution, diversity, and clinical significance of neurotoxic snake venoms in Mexico.