La inhibición de la gamma secretasa altera la expresión de genes de la vía de señalización Notch en el cisticerco de Taenia solium y reprime la evaginación del escólex

• Autor: Blume La Torre, Juan
• Formato: tesis de maestría
• Fecha de Publicación: 2020
• Institución: Universidad Peruana Cayetano Heredia
• Repositorio: UPCH-Institucional
• Lenguaje: español
• OAI Identifier: oai:repositorio.upch.edu.pe:20.500.12866/8940
• Enlace del recurso: https://hdl.handle.net/20.500.12866/8940
• Nivel de acceso: acceso abierto
• Materia: Taenia solium; Evaginación; Vía de Señalización Notch; DAPT; https://purl.org/pe-repo/ocde/ford#1.06.03; https://purl.org/pe-repo/ocde/ford#3.03.07; https://purl.org/pe-repo/ocde/ford#3.03.08

The cestode Taenia solium, the causative agent of neurocysticercosis, can be an intestinal flatworm or a larval cyst that lodges in soft tissues like the brain. The cyst stage is an invaginated, underdeveloped worm inside a 10-15 mm vesicle. If a person ingests a cyst, present in infected pork meat, gastric juices stimulate the evagination of the “head” or scolex, initiating the metamorphoses into the adult form. The worm can grow up to 3 meters, forming proglottids. These mature sexually and produce eggs that are expelled in feces and can contaminate water sources and food. Eggs ingested by pigs or humans develop as cysts, closing the life cycle of the parasite. The Notch pathway is involved in developmental processes such as tissue patterning, sexual maturation, and neural development. Since Notch genes participate in the body patterning and segmentation of the cestode Hymenolepis microstoma, we tested if this pathway had a role in the evagination of T. solium, as an initial and determining event in development. Groups of cysts were cultured in the presence of taurocholic acid (TA), to induce evagination, or DAPT, to inhibit the gamma secretase and indirectly Notch signaling. After five days, 92% of the cysts treated with TA had evaginated the scolex; the induced juvenile worms showed increased expression of the notch1 receptor, measured by RT-qPCR. Conversely, 93% of the cysts treated with DAPT for five days failed to evaginate the scolex. Cysts cultivated in the inhibitor's presence had reduced mRNA level of notch1 and increased mRNA level of the target gene hes2. The gamma secretase inhibitor prevented in vitro evagination and changed the expression of genes from the Notch pathway. These results encourage the search for targets to arrest the development and sexual maturation of T. solium into the disseminative stage of the parasite.