Delgado M, Anderson P, Garcia-Salcedo J A, Caro M, Gonzalez-Rey E
Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada, Spain.
Cell Death Differ. 2009 Mar;16(3):406-16. doi: 10.1038/cdd.2008.161. Epub 2008 Dec 5.
Trypanosoma brucei is the causative agent of African sleeping sickness. Available treatments are ineffective, toxic and susceptible to resistance by the parasite. Here we show that various endogenous neuropeptides act as potent antitrypanosome agents. Neuropeptides exerted their trypanolytic activity through an unusual mechanism that involves peptide uptake by the parasite, disruption of lysosome integrity and cytosolic accumulation of glycolytic enzymes. This promotes an energetic metabolism failure that initiates an autophagic-like cell death. Neuropeptide-based treatment improved clinical signs in a chronic model of trypanosomiasis by reducing the parasite burden in various target organs. Of physiological importance is the fact that hosts respond to trypanosome infection producing neuropeptides as part of their natural innate defense. From a therapeutic point of view, targeting of intracellular compartments by neuropeptides suppose a new promising strategy for the treatment of trypanosomiasis.
布氏锥虫是非洲昏睡病的病原体。现有的治疗方法无效、有毒且易被寄生虫产生耐药性。在此我们表明，多种内源性神经肽可作为有效的抗锥虫剂。神经肽通过一种不同寻常的机制发挥其溶锥虫活性，该机制涉及寄生虫对肽的摄取、溶酶体完整性的破坏以及糖酵解酶的胞质积累。这会导致能量代谢衰竭，引发类似自噬的细胞死亡。基于神经肽的治疗通过减轻各种靶器官中的寄生虫负担，改善了锥虫病慢性模型中的临床症状。具有生理重要性的是，宿主对锥虫感染会产生神经肽作为其天然固有防御的一部分。从治疗角度来看，神经肽靶向细胞内区室为锥虫病的治疗提供了一种新的有前景的策略。
