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Proteínas del sistema inmunológico: clave para comprender la enfermedad de Huntington
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La enfermedad de Huntington, un trastorno neurodegenerativo controlado por un solo gen, ha sido objeto de una nueva investigación del Boston Children’s Hospital que ofrece esperanza para la protección del cerebro y la prevención o retraso del deterioro cognitivo. Los hallazgos, publicados recientemente en Nature Medicine, sugieren que las proteínas del complemento y la microglía, partes del sistema inmunológico, podrían ser clave en la pérdida de sinapsis específicas que conectan la corteza y el cuerpo estriado del cerebro.
El laboratorio de Beth Stevens, Ph.D., ha sido pionero en la comprensión de cómo la microglía, las células inmunes del cerebro, engulle y poda las sinapsis durante el desarrollo normal del cerebro. Ahora, han demostrado que este proceso de poda se reactiva anormalmente en enfermedades neurodegenerativas como la enfermedad de Huntington, la enfermedad de Alzheimer y la esquizofrenia.
Utilizando un modelo animal y muestras cerebrales post mortem de pacientes con enfermedad de Huntington, los investigadores descubrieron que las proteínas del complemento y la microglía se activan en las primeras etapas de la enfermedad, mucho antes de que aparezcan los síntomas cognitivos y motores. Estas proteínas se concentran en un circuito cerebral específico que conecta la corteza y el cuerpo estriado, regiones cerebrales afectadas en las primeras etapas de la enfermedad.
Bloqueo de la proteína del complemento C1q
Al bloquear la proteína del complemento C1q en el modelo animal, ya sea con un anticuerpo o eliminando genéticamente el receptor del complemento CR3 en la microglía, los investigadores lograron prevenir la pérdida de sinapsis y los defectos cognitivos relacionados con el aprendizaje y la flexibilidad cognitiva.
Según Dan Wilton, Ph.D., autor principal del estudio, “En la enfermedad de Huntington, es común que los déficits cognitivos aparezcan mucho antes que los defectos motores, y esto también se observa en los seres humanos”. Además, Wilton señala que el modelo de enfermedad de Huntington que están investigando muestra la presencia de defectos motores leves, los cuales también pueden ser resueltos mediante el uso de estrategias de bloqueo del complemento.
Intervenciones tempranas en la enfermedad de Huntington
Estos hallazgos podrían tener un impacto significativo en el desarrollo de intervenciones tempranas para la enfermedad de Huntington. Además, los niveles elevados de moléculas inmunes innatas en el líquido cefalorraquídeo de los pacientes con enfermedad de Huntington podrían servir como un biomarcador para estratificar a las personas en las etapas más tempranas de la enfermedad y priorizar su tratamiento.
Beth Stevens y su equipo también creen que estos mecanismos y biomarcadores podrían aplicarse a otros trastornos neurodegenerativos, como el Alzheimer y la demencia frontotemporal. Con estos descubrimientos, se abre una nueva dirección de investigación para comprender cómo la mutación de la Huntingtina, la proteína asociada con la enfermedad de Huntington, conduce a la activación del complemento y qué factores desencadenan la selección de los aportes corticoestriatales.
La lucha contra la enfermedad de Huntington ha dado un paso importante hacia la comprensión de sus mecanismos y la identificación de posibles intervenciones tempranas. Estos avances podrían tener un impacto significativo en la vida de las personas afectadas por esta enfermedad y allanar el camino hacia tratamientos más efectivos en el futuro.
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