Proliferative cells in racemose neurocysticercosis have an active MAPK signalling pathway and respond to metformin treatment. Issue 6 (May 2022)

• Record Type: Journal Article
• Authors: Orrego, Miguel A.; Verastegui, Manuela R.; Vasquez, Carlos M.; Garcia, Hector H.; Nash, Theodore E.
• Is Part Of: International journal for parasitology. Volume 52:Issue 6(2022)
• Page Start: 377
• Page End: 383
• Publication Date: 2022-05
• Subjects: Cisticercosis -- Neurocysticercosis -- Subarachnoid cyst -- Taenia solium -- MAPK; Parasitology -- Periodicals; Parasitology -- Periodicals; Parasitologie -- Périodiques; Parasitology; Periodicals; Electronic journals; 571.999
• DOI: 10.1016/j.ijpara.2022.01.001
• Languages: English
• ISSNs: 0020-7519

Abstract

Graphical abstract: Highlights: Racemose neurocysticercosis is the most severe and difficult to treat form of extra-parenchymal neurocysticercosis. The bladder wall of the racemose cyst has an active MAPK signalling pathway compared with the vesicular cyst. Metformin reduces the proliferation of the bladder wall targeting proliferative cells of the parasite in vitro and in vivo. Use of metformin for the treatment of racemose NCC represents an attractive alternative that requires further evaluation. Abstract: Racemose neurocysticercosis is an aggressive infection caused by the aberrant expansion of the cyst form of Taenia solium within the subarachnoid spaces of the human brain and spinal cord, resulting in the displacement of the surrounding host tissue and chronic inflammation. We previously demonstrated that the continued growth of the racemose bladder wall is associated with the presence of mitotically active cells but the nature and control of these proliferative cells are not well understood. Here, we demonstrated by immunofluorescence that the racemose cyst has an active mitogen-activated protein kinases (MAPK) signalling pathway that is inhibited after treatment with metformin, which reduces racemose cell proliferation in vitro, and reduces parasite growth in the murine model of Taenia crassiceps cysticercosis. Our findings indicate the importance of insulin receptor-mediated activation of the MAPK signalling pathway in the proliferation and growth of the bladder wall of the racemose cyst and its susceptibility to metformin action. The antiproliferative action of metformin may provide a new therapeutic approach against racemose neurocysticercosis.