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 Chiropsalmus quadrumanus (Cq) on neurites. The Cq 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 Cq 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 Cq extract is a promising tool for neuronal connection recovery, an essential condition for the treatment of neurodegenerative diseases.

中文翻译：

---

箱形水母（刺胞动物、立方动物）提取物可增加神经元的连接：可能具有神经保护作用


神经退行性疾病是全世界死亡的主要原因之一，其特征是神经突萎缩、神经元凋亡和突触损失。迄今为止，还没有针对此类疾病的有效治疗方法，并且近年来对新药的寻找正在增加。动物毒液的分泌物/毒液可以作为发现新分子的替代方案，这可能是新疗法的原型。在这里，我们介绍了箱形水母Chiropsalmusquadramanus ( Cq ) 提取物对神经突的生化特征和活性。获得Cq甲醇提取物并与人 SH-SY5Y 神经元一起孵育，并评估神经突参数。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，并通过质谱法进行生化分析，以检查其成分。我们可以验证Cq提取物增加了神经突生长长度和分支连接，放大了 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（例如肿瘤细胞系、非肿瘤细胞系和红细胞）造成任何影响。此外，质谱分析表明，其中不存在蛋白质，而是几种低分子量化合物和肽。三种肽（特征为隐肽）和 14 种低分子量化合物被发现与细胞骨架重组、细胞膜扩张和抗氧化/神经保护活性相关，它们共同作用以增加神经突发生。 经过评估，我们得出结论， Cq提取物是神经元连接恢复的有前途的工具，神经元连接恢复是治疗神经退行性疾病的必要条件。