Proteínas del estadío larval de Taenia solium inducen daño neuronal y activan la vía MAPK

Abstract

Introduction: Neurocysticercosis (NCC), caused by Taenia solium larval stage, is one of the leading neurological diseases in Latin America and is associated with neuronal damage with the formation of axonal swellings characterized by the accumulation of proteins such as neurofilament and APP. In other neurological disorders, the mitogen-activated protein kinase (MAPK) signaling pathway has been implicated in neuronal damage. In this context, the overall objective of this study was to determine the role of the MAPK signaling pathway in neuronal damage induced by excretory/secretory (E/S) proteins from the larval stage of T. solium in primary cultures of rat hippocampal neurons. Methodology: E/S proteins were obtained from cysticerci isolated from porcine tissue, concentrated, and separated into 22 fractions by ion exchange chromatography. Primary cultures of rat hippocampal neurons were exposed to these fractions to quantify axonal damage. Some neurotoxic protein fractions were characterized by mass spectrometry, and activation of the MAPK pathways (ERK, JNK, and p38) was assessed by Western blot analysis. Results: Fractions F2, F8, F16, F17, F20, and F21 were identified as inducers of axonal swellings, with F20 and F21 producing the most severe effects. Proteomic analysis of fractions F8 and F20 revealed 12 shared proteins, including nardilysin, calreticulin, and PSA. E/S proteins activated MAPK pathways in a defined temporal sequence: ERK (at 10–20 min), p38 (30 min), and JNK (45 min). Specifically, fraction F8 preferentially activated the JNK pathway, whereas fraction F20 activated both ERK and JNK. Conclusion: T. solium secrete proteins that cause neuronal damage and activation of the MAPK pathways. These findings challenge the paradigm that neuronal damage in NCC is purely immune-mediated and instead suggest that the parasite could activate endogenous stress and cell death pathways, to induce an irreversible neurodegenerative program.

Introduction: Neurocysticercosis (NCC), caused by Taenia solium larval stage, is one of the leading neurological diseases in Latin America and is associated with neuronal damage with the formation of axonal swellings characterized by the accumulation of proteins such as neurofilament and APP. In other neurological disorders, the mitogen-activated protein kinase (MAPK) signaling pathway has been implicated in neuronal damage. In this context, the overall objective of this study was to determine the role of the MAPK signaling pathway in neuronal damage induced by excretory/secretory (E/S) proteins from the larval stage of T. solium in primary cultures of rat hippocampal neurons. Methodology: E/S proteins were obtained from cysticerci isolated from porcine tissue, concentrated, and separated into 22 fractions by ion exchange chromatography. Primary cultures of rat hippocampal neurons were exposed to these fractions to quantify axonal damage. Some neurotoxic protein fractions were characterized by mass spectrometry, and activation of the MAPK pathways (ERK, JNK, and p38) was assessed by Western blot analysis. Results: Fractions F2, F8, F16, F17, F20, and F21 were identified as inducers of axonal swellings, with F20 and F21 producing the most severe effects. Proteomic analysis of fractions F8 and F20 revealed 12 shared proteins, including nardilysin, calreticulin, and PSA. E/S proteins activated MAPK pathways in a defined temporal sequence: ERK (at 10–20 min), p38 (30 min), and JNK (45 min). Specifically, fraction F8 preferentially activated the JNK pathway, whereas fraction F20 activated both ERK and JNK. Conclusion: T. solium secrete proteins that cause neuronal damage and activation of the MAPK pathways. These findings challenge the paradigm that neuronal damage in NCC is purely immune-mediated and instead suggest that the parasite could activate endogenous stress and cell death pathways, to induce an irreversible neurodegenerative program.