Kularatne S A M, Senanayake Nimal
Department of Medicine, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka.
Department of Medicine, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka.
Handb Clin Neurol. 2014;120:987-1001. doi: 10.1016/B978-0-7020-4087-0.00066-8.
Neurologic dysfunction due to natural neurotoxins is an important, but neglected, public health hazard in many parts of the world, particularly in the tropics. These toxins are produced by or found among a variety of live forms that include venomous snakes, arthropods such as scorpions, spiders, centipedes, stinging insects (Hymenoptera), ticks, certain poisonous fish, shellfish, crabs, cone shells, skin secretions of dart-poison frogs, and bacterial poisons such as botulinum toxin. These toxins commonly act on neuromuscular transmission at the neuromuscular junction where acetylcholine is the neurotransmitter, but in certain situations the toxins interfere with neurotransmitters such as GABA, noradrenaline, adrenaline, dopamine, and γ-aminobutyrate. Of the toxins, α-toxins and κ-toxins (e.g., Chinese krait, Bungarus multicinctus) act on the postsynaptic membrane, blocking the receptors, whilst β-toxin (e.g., common krait, B. caeruleus) acts on the presynaptic membrane, causing impairment of acetylcholine release. Conversely, dendrotoxins of the African mamba enhance acetylcholine release. The toxins of scorpions and spiders commonly interfere with voltage-gated ion channels. Clinically, the cardinal manifestation is muscle paralysis. In severe cases respiratory paralysis could be fatal. Effective antivenoms are the mainstay of treatment of envenoming, but their lack of availability is the major concern in the regions of the globe where they are desperately needed. Interestingly, some toxins have proved to be valuable pharmaceutical agents, while some others are widely exploited to study neuromuscular physiology and pathology.
在世界许多地区,尤其是热带地区,天然神经毒素导致的神经功能障碍是一个重要但被忽视的公共卫生危害。这些毒素由多种生物产生或存在于多种生物之中,包括毒蛇、蝎子、蜘蛛、蜈蚣、叮咬昆虫(膜翅目)、蜱、某些有毒鱼类、贝类、螃蟹、芋螺、箭毒蛙的皮肤分泌物以及肉毒杆菌毒素等细菌毒素。这些毒素通常作用于神经肌肉接头处的神经肌肉传递,此处乙酰胆碱是神经递质,但在某些情况下,毒素会干扰γ-氨基丁酸、去甲肾上腺素、肾上腺素、多巴胺和γ-氨基丁酸盐等神经递质。在这些毒素中,α-毒素和κ-毒素(如中国银环蛇,多环银环蛇)作用于突触后膜,阻断受体,而β-毒素(如普通银环蛇,孟加拉银环蛇)作用于突触前膜,导致乙酰胆碱释放受损。相反,非洲树眼镜蛇的树眼镜蛇毒素可增强乙酰胆碱释放。蝎子和蜘蛛的毒素通常会干扰电压门控离子通道。临床上,主要表现为肌肉麻痹。严重时呼吸麻痹可能致命。有效的抗蛇毒血清是治疗蛇咬伤的主要手段,但在急需它们的全球区域,抗蛇毒血清供应不足是主要问题。有趣的是,一些毒素已被证明是有价值的药物制剂,而其他一些毒素则被广泛用于研究神经肌肉生理学和病理学。