Beyond Venom and Constriction: Bite Performance and Trophic Ecology in the Genus Drymarchon

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  Beyond Venom and Constriction: Bite Performance and Trophic Ecology in the Genus Drymarchon Abstract Snakes exhibit extreme cranial kinesis that facilitates ingestion of prey with large cross-sectional area, but this ability is widely predicted to reduce bite performance due to decreased structural rigidity. Consequently, most large-bodied snakes rely on envenomation or constriction to subdue prey prior to ingestion. Species within the genus Drymarchon represent a notable exception: these large, non-venomous, non-constricting snakes routinely consume a wide range of prey, including large and potentially dangerous vertebrates, using only simple seizing and pinioning behaviors. Here, we quantify bite performance in three species of Drymarchon ( D. corais, D. couperi, and D. melanurus ), examine morphological predictors of biting performance, compare biting pressure to constriction pressure in similarly sized snakes, and synthesize dietary records across the genus. Our results sh...

Cobrotoxin suppresses TLR4-NF-κB/STAT1 signaling to mitigate glia-mediated neuroinflammation and motor deficits in Parkinson's disease

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Cobrotoxin suppresses TLR4-NF-κB/STAT1 signaling to mitigate glia-mediated neuroinflammation and motor deficits in Parkinson's disease

Abstract

Chronic neuroinflammation is implicated in the pathogenesis of Parkinson's disease (PD), contributing to progressive dopaminergic neuron loss. Cobrotoxin (CoTX), a short-chain α-neurotoxin isolated from Naja atra venom, exerts anti-inflammatory and analgesic effects in several inflammation-related disease models. However, whether CoTX modulates glia-mediated neuroinflammation or confers neuroprotection in PD remains unknown. In this study, we conducted a randomized, placebo-controlled clinical trial and preclinical animal studies to explore the therapeutic efficacy and mechanisms of CoTX in PD. A 12-day subcutaneous regimen of Cobratide (an injectable form of CoTX), consisting of 70 μg daily for 5 days, a 2-day interval, and another 5-day course, significantly improved motor symptoms in PD patients, as reflected by the UPDRS Part II + III scores, with a well-tolerated safety profile. These beneficial effects were further validated in both MPTP- and lipopolysaccharide-induced PD mouse models. Specifically, intranasal administration of CoTX ameliorated motor coordination defects, attenuated dopaminergic neuronal loss, and suppressed glia-mediated neuroinflammation in the substantia nigra of MPTP-challenged mice. Mechanistically, CoTX did not directly protect neurons; instead, it conferred indirect neuroprotection by inhibiting neuroinflammation via blockade of the NF-κB/STAT1 signaling cascades. Furthermore, CoTX functionally interacted with TLR4, which may act as a putative molecular target of CoTX. Collectively, these findings demonstrate the anti-neuroinflammatory and neuroprotective effects of CoTX in PD, highlighting its potential as a promising therapeutic candidate.
Yu, C., Ma, S., Cao, Y., Xu, D., Hou, X., Liu, C., Qin, Z., Luo, W., Wu, J., Liu, J., & Hu, L. (2026). Cobrotoxin suppresses TLR4-NF-κB/STAT1 signaling to mitigate glia-mediated neuroinflammation and motor deficits in Parkinson's disease. International Immunopharmacology, 188, 117322. https://doi.org/10.1016/j.intimp.2026.117322