Martins N M, Santos N A G, Sartim M A, Cintra A C O, Sampaio S V, Santos A C
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - USP, Av. do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - USP, Av. do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
Chem Biol Interact. 2015 Jun 25;235:10-6. doi: 10.1016/j.cbi.2015.04.004. Epub 2015 Apr 10.
Parkinson's disease (PD) is the second most common neurodegenerative disorder; however, there is no treatment able to prevent the loss of dopaminergic neurons or its consequences. Trophic factors such as NGF and BDNF has positive effects on different disorders of the brain, including neurodegeneration. Additionally, studies have suggested the use of venom peptides as a therapeutic strategy for neurological disorders. Therefore, in the present study, we investigated the neuroprotective activity of a peptide isolated from Bothrops atrox venom and its trophic ability by using a cellular model of dopaminergic neurotoxicity induced by 1-methyl-4-phenylpyridinium (MPP(+)) in PC12 cells. We showed that it decreased the activities of the apoptotic proteases caspase-9 (mitochondrial) and caspase-3 (executor) and increased cell viability and proliferation in this model. Additionally, it increased neuritogenesis in non-treated PC12 cells (neuronal model) as well as in PC12 cells treated with the dopaminergic neurotoxin. The amino acid sequence of the peptide was identified as Glutamic acid-Valine-Tryptophan (Glu-Val-Trp). These findings suggest that this tripeptide has the potential to protect against the dopaminergic neurons loss and that trophic stimulation of neuroplasticity might be involved in its mechanism of neuroprotection.
帕金森病（PD）是第二常见的神经退行性疾病；然而，目前尚无能够预防多巴胺能神经元丧失或其后果的治疗方法。神经营养因子如神经生长因子（NGF）和脑源性神经营养因子（BDNF）对包括神经退行性变在内的不同脑部疾病具有积极作用。此外，研究表明使用毒液肽作为神经疾病的治疗策略。因此，在本研究中，我们通过使用1-甲基-4-苯基吡啶鎓（MPP(+)）诱导的PC12细胞多巴胺能神经毒性细胞模型，研究了从矛头蝮蛇毒液中分离出的一种肽的神经保护活性及其营养能力。我们发现，在该模型中，它降低了凋亡蛋白酶caspase-9（线粒体）和caspase-3（执行器）的活性，并提高了细胞活力和增殖能力。此外，它还增加了未处理的PC12细胞（神经元模型）以及用多巴胺能神经毒素处理的PC12细胞中的神经突生长。该肽的氨基酸序列被鉴定为谷氨酸-缬氨酸-色氨酸（Glu-Val-Trp）。这些发现表明，这种三肽具有预防多巴胺能神经元丧失的潜力，并且神经可塑性的营养刺激可能参与其神经保护机制。
