Información del artículo
Resumen
El síndrome de Hutchinson-Gilford es un síndrome progeroide que se caracteriza por un envejecimiento acelerado que comienza tempranamente en la infancia. El estudio de células de pacientes y el desarrollo de modelos animales (Zmpste24–/–, Zmpste24–/–Lmna+/–, LmnaLCO/LCO que reproducen esta dolencia ha aportado nuevos conocimientos para entender las bases genéticas de esta enfermedad y así también profundizar en las del envejecimiento fisiológico.
El fenotipo característico de este síndrome se debe a alteraciones en la lamina nuclear, estructura formada por un conjunto de filamentos intermedios (laminas A, B y C) que permiten mantener la organización de la envoltura nuclear. Se ha demostrado que una mutación del gen LMNA, que sintetiza la lamina A, es la del depósito de lamina A farnesilada (progerina) que es la causante de las alteraciones en la envoltura nuclear y del fenotipo de este raro síndrome. El empleo de moléculas que actúan sobre diferentes pasos en la síntesis de progerina se está revelando como un futuro terapéutico prometedor para revertir los efectos nocivos de su síntesis.
Palabras clave:
Envoltura nuclear
Laminopatías
Envejecimiento acelerado
Hutchinson-Gilford disease is a progeroid syndrome characterized by accelerated ageing beginning in early childhood. Study of several types of cells from patients with this syndrome and the development of animal models (Zmpste24–/–, Zmpste24–/–Lmna+/–, LmnaLCO/LCO) that mimic this disease have increased knowledge of the genetic foundations of this rare entity and those of normal ageing.
The phenotypic features of this syndrome are caused by alterations in the fibrillar components of the nuclear lamina (lamins A, B, and C), which maintain the structure of the nuclear envelope. A point mutation in the gene for lamin A (LMNA) induces deposit of a farnesylated lamin A (progerin), which causes the nuclear alterations observed in the affected cells. The use of several molecules that interfere with progerin synthesis has been proposed as a promising potential therapeutic approach to reverse the adverse effects of progerin synthesis.
Key words:
Nuclear envelope
Laminopathies
Accelerated ageing
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