Targeting CRM1 for Progeria Syndrome Therapy.

Adriana Soto-Ponce, Marlon De Ita, Susana Castro-Obregón, Diego Cortez, Yosef Landesman, Jonathan J Magaña, Susana Gonzalo, Tania Zavaleta, Angelica Soberano-Nieto, Juan Unzueta, Isabel Arrieta-Cruz, Porfirio Nava, Aurora Candelario-Martínez, Ian García-Aguirre, Bulmaro Cisneros

Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados, Ciudad de México, Mexico.Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados, Ciudad de México, Mexico. · pubmed

Paper

Abstract

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused by progerin, a mutant variant of lamin A. Progerin anchors aberrantly to the nuclear envelope disrupting a plethora of cellular processes, which in turn elicits senescence. We previously showed that the chromosomal region maintenance 1 (CRM1)-driven nuclear export pathway is abnormally enhanced in patient-derived fibroblasts, due to overexpression of CRM1. Interestingly, pharmacological inhibition of CRM1 using leptomycin B rescues the senescent phenotype of HGPS fibroblasts, delineating CRM1 as a potential therapeutic target against HGPS. As a proof of concept, we analyzed the beneficial effects of pharmacologically modulating CRM1 in dermal fibroblasts from HGPS patients and the LMNA

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Research summary

Pharmacological inhibition of CRM1 rescues the senescent phenotype of Hutchinson-Gilford progeria syndrome fibroblasts. This research addresses a specific aging-related disease by targeting a mechanism that contributes to cellular senescence, which is a key aspect of the aging process.

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