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Exploiting animal toxins to probe molecular mechanisms of pain

  • Author(s): Zhang, Chuchu
  • Advisor(s): Julius, David
  • Basbaum, Allan I
  • et al.
Abstract

Venoms from spiders, snakes, cone snails and scorpions have evolved to produce a

vast pharmacopoeia of toxins that modulate receptor or channel function as a means of

producing shock, hemolysis, paralysis and pain. As such, venoms from these animals

represent a rich potential source of potent and selective toxins that can be exploited to

study and manipulate somatosensory and nociceptive signaling pathways. In this work, I

have identified and characterized two novel toxins from the Brazilian lancehead pit viper

(Bothrops moojeni) and Tanzania blue ringleg centipede (Scolopendra morsitans). The

Brazilian lancehead snake venom contains a novel secreted phospholipase A2

(sPLA2)-like protein that can promote ATP release from pannexin hemichannels.

Studies on the cellular and behavioral effects of this toxin reveal a role of regulated

endogenous nucleotide release in nociception. The discovered Tanzania blue ringleg

centipede toxin represents a new family of toxins that show evolutionary relationship

with α-scorpion toxins and could potentially function as potassium channel blockers.

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