Vélez AG, Cisneros VB

Idioma: Español
Referencias bibliográficas: 79
Paginas: 27-38
Archivo PDF: 323.07 Kb.

RESUMEN

Las distrofias musculares del humano se deben a la ausencia o mal funcionamiento de proteínas esenciales para el tejido muscular. Un grupo importante está relacionado con mutaciones en genes que codifican para los miembros del complejo de proteínas asociadas a la distrofina (DAPC). El DAPC comunica la matriz extracelular con el citoesqueleto y le confiere estabilidad al sarcolema durante los ciclos de contracción-relajación. Un componente primordial de este ensamblaje proteico es el distroglicano, el cual es codificado por el gen DAG1 y procesado postraduccionalmente para generar dos subunidades: la proteína transmembranal β-distroglicano (β-DG) y la proteína extracelular α-distroglicano (α-DG). Los distroglicanos conectan la matriz extracelular con el citoesqueleto de actina, ya que el β-DG se une a la distrofina y ésta, a su vez, con la actina, mientras que el α-DG interacciona con la proteína de matriz extracelular laminina y conecta, al mismo tiempo, con el β-DG. La glicosilación del α-DG le confiere la capacidad de asociarse con la matriz extracelular. De manera relevante, una serie particular de distrofias musculares, denominadas «distroglicanopatías» se origina precisamente por defectos en la glicosilación del α-DG. Las distroglicanopatías primarias se deben a mutaciones puntuales homocigotas en el gen DAG1, mientras que las distroglicanopatías secundarias son causadas por mutaciones en al menos 15 genes que codifican para enzimas implicadas en la vía de glicosilación del α-DG. Entre las distroglicanopatías más estudiadas se encuentran el síndrome de Walker-Warburg, el desorden muscular músculo-ojos-cerebro, la distrofia muscular congénita de Fukuyama, las distrofias musculares congénitas 1C y 1D, y la distrofia muscular de cintura. En esta revisión, describimos las manifestaciones clínicas de las diferentes distroglicanopatías y presentamos una visión actual de las bases genéticas y moleculares que subyacen estas patologías. En la parte final, describimos los modelos animales que se han generado para el estudio de las distroglicanopatías y el incipiente desarrollo de terapias para combatirlas.

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