Laboratório Multidisciplinar de Pesquisa, Universidade São Francisco, Bragança Paulista 12916-900, Brazil.
Laboratório de Genética, Instituto Butantan, São Paulo 05503-900, Brazil.
Biomed Res Int. 2021 Mar 4;2021:8855248. doi: 10.1155/2021/8855248. eCollection 2021.
Neurodegenerative diseases are one of the major causes of death worldwide, characterized by neurite atrophy, neuron apoptosis, and synapse loss. No effective treatment has been indicated for such diseases so far, and the search for new drugs is being increased in the last years. Animal venoms' secretion/venom can be an alternative for the discovery of new molecules, which could be the prototype for a new treatment. Here, we present the biochemical characterization and activity of the extract from the box jellyfish () on neurites. The methanolic extract was obtained and incubated to human SH-SY5Y neurons, and neurite parameters were evaluated. The extract was tested in other cell types to check its cytotoxicity and was submitted to biochemical analysis by mass spectrometry in order to check its composition. We could verify that the extract increased neurite outgrowth length and branching junctions, amplifying the contact between SH-SY5Y neurons, without affecting cell body and viability. The extract action was selective for neurons, as it did not cause any effects on other cell types, such as tumor line, nontumor line, and red blood cells. Moreover, mass spectrometry analysis revealed that there are no proteins but several low molecular mass compounds and peptides. Three peptides, characterized as cryptides, and 14 low molecular mass compounds were found to be related to cytoskeleton reorganization, cell membrane expansion, and antioxidant/neuroprotective activity, which act together to increase neuritogenesis. After this evaluation, we conclude that the extract is a promising tool for neuronal connection recovery, an essential condition for the treatment of neurodegenerative diseases.
神经退行性疾病是全球主要死亡原因之一，其特征为轴突萎缩、神经元凋亡和突触丧失。目前尚无有效的治疗方法，近年来人们越来越多地在寻找新的药物。动物毒液的分泌/毒液可以作为发现新分子的替代物，这些新分子可能成为新疗法的原型。在这里，我们展示了箱型水母 () 的提取物对轴突的生化特征和活性。获得了该提取物，并将其孵育到人类 SH-SY5Y 神经元中，评估了轴突参数。该提取物在其他细胞类型中进行了测试，以检查其细胞毒性，并通过质谱分析进行了生化分析，以检查其组成。我们可以验证该提取物增加了轴突的生长长度和分支连接，扩大了 SH-SY5Y 神经元之间的接触，而不影响细胞体和活力。提取物的作用对神经元具有选择性，因为它不会对其他细胞类型（如肿瘤系、非肿瘤系和红细胞）产生任何影响。此外，质谱分析表明，该提取物中没有蛋白质，而是含有几种低分子量化合物和肽。发现了三种被表征为 cryptides 的肽和 14 种与细胞骨架重组、细胞膜扩张和抗氧化/神经保护活性相关的低分子量化合物，它们共同作用以增加轴突发生。经过评估，我们得出结论，该提取物是恢复神经元连接的有前途的工具，这是治疗神经退行性疾病的必要条件。
