Investigadores revelan la existencia de un mecanismo celular inusual que podría fallar en pacientes con el mal de Alzheimer. ¿Por qué una célula se tomaría el trabajo de destruir proteínas perfectas y recientemente producidas?
Una nueva investigación sugiere que este inusual mecanismo celular podría, entre otras cosas, fallar en pacientes con el mal de Alzheimer.
La investigación fue realizada por el Instituto Weizmann conjuntamente con centros de investigación en Alemania, y fue publicada en Molecular Cell.
La Dra. Maya Schuldiner y el estudiante de investigación Dr. Shai Fuchs del Departamento de Genética Molecular del Instituto Weizmann, en colaboración con el Dr. Marius Lemberg y el Dr. Donem Avci de la Universidad de Heidelberg, investigaron la Presenilina, una proteína humana que se encuentra mutada en una forma familiar de Alzheimer en edad temprana.
Para investigar el mecanismo de esta proteína, los científicos estudiaron un ancestro de la Presenilina, una proteína de la levadura que identificaron como Ypf1 (por sus siglas en inglés de “pliegue de la Presenilina de la levadura 1”), que se ha conservado durante la evolución.
La remoción de la Ypf1 de las células de levadura, resultó en un incremento excesivo de una proteína cuya función es bombear Zinc – un metal esencial – hacia el interior de la célula. Lo extraño es que a pesar de la existencia de dos proteínas que bombean zinc hacia el interior de la célula, sólo una fue afectada.
La proteína incrementada es una bomba “turbo” o de alta afinidad, mientras que la proteína no afectada es principalmente una bomba de “uso diario”, de baja afinidad. Al igual que la Presenilina, la Ypf1 es una proteasa – una proteína que degrada otras proteínas. Por lo tanto, los investigadores concluyeron que su función es eliminar de la célula las bombas “turbo” transportadoras de zinc.
De hecho, ellos se percataron que estaban estudiando un tipo de sistema a dos bombas, que fue descrito muchos años atrás por la Prof. Naama Barkai del Instituto Weizmann.
Las bombas de nutrientes de baja afinidad podrán no ser muy eficientes en el transporte de nutrientes hacia la célula, pero son muy sensibles a cambios en los niveles de dichos nutrientes.
Cuando estos bajan, ellas inician un protocolo de emergencia.
Los transportadores de alta afinidad pueden ser activados para crear reservas de nutrientes ante una cercana época de “escasez”. Sin embargo, estas bombas no pueden activar el sistema de emergencia.
En este escenario, células saludables deben trabajar la mayor parte del tiempo sobre las bombas estándar (“de uso diario”), permitiendo a las bombas “turbo” alcanzar la superficie celular sólo en tiempos de necesidad.
Los investigadores se preguntaron cómo un exceso de bombas “turbo” en la superficie de la célula podría afectar la habilidad de las células para prepararse para tiempos de escasez.
De hecho, las células deficientes en Ypf1 tardaron mucho en detectar la falta de nutrientes, por lo que fueron muy ineficientes ante la falta zinc, y les tomó más tiempo recuperase.
No sólo las bombas de zinc son afectadas. Los investigadores mostraron que la falta de Ypf1 causa un desbalance en bombas de alta afinidad transportadoras de muchos otros nutrientes.
“La producción continua de transportadores de alta afinidad y su posterior degradación es un tipo de mecanismo de doble seguridad que las células desarrollaron para garantizar la estabilidad de los niveles de nutrientes vitales como el zinc dentro de la célula”, dice Fuchs.
“A pesar de que aún no sabemos exactamente en seres humanos cuál es la relación entre este mecanismo y el Alzheimer, existen evidencias interesantes de que el transporte de zinc en particular, así como el de los metales en general, podría tener un papel clave en el comienzo y progreso de la enfermedad.
Estamos emocionados ya que esta nueva pista podría representar un indicio de causas aún no entendidas del mal de Alzheimer.
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