Erratum - Autophagic Degradation of Farnesylated Prelamin a as a Therapeutic Approach to Lamin-Linked Progeria

V. Cenni,1 C. Capanni,1 M. Columbaro,2 M. Ortolani,1 M.R. D’Apice,3 G. Novelli,4 M. Fini,5 S. Marmiroli,6 E. Scarano,7 N.M. Maraldi,2 S. Squarzoni,1 S. Prencipe,5 G. Lattanzi1 1National Research Council of Italy, Institute for Molecular Genetics, IGM-CNR, Unit of Bologna c/o IOR, Bologna 2Laboratory of Musculoskeletal Cell Biology, Rizzoli Orthopedic Institute, Bologna 3Department of Biopathology and Diagnostic Imaging Tor Vergata University, Rome 4National Agency for the Evaluation of Universities and Research, ANVUR, Rome Italy and San Pietro Fatebenefratelli Hospital, Rome 5Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute and BITTA, RIT, IOR, Bologna 6Department of Histology, University of Modena and Reggio Emilia, Modena 7Department of Pediatrics, S. OrsolaMalpighi Hospital, University of Bologna, Italy We refer to our article by Vittoria Cenni et al. published in the European Journal of Histochemistry.1 We have observed that Figure 1 A and Figure 2 A were not adequate to clearly represent the results we report in the paper. Therefore, we have replaced the pictures with better versions of images reporting the same experiments. In Figure 1A we show that degradation of the mutated prelamin A form called progerin in Hutchinson-Gilford progeria fibroblasts is obtained using rapamycin and it is driven through the lysosomal pathway, as demonstrated by LC3 2B activation. In Figure 2A, we support the data showing that the whole platform of nuclear envelope/lamina partners is positively affected by reduction of progerin elicited by rapamycin treatment. The results reported in our paper are consistent with those shown in 2011 by Cao and co-workers on Science Translational Medicine.2 The efficacy of rapamycin in progeria cells prompted a group of clinicians in the American Progeria Research Foundation to include rapamycin in an upcoming clinical trial. Our paper further shows that the efficacy of rapamycin in progeria cells is due to its ability to restore key chromatin partners of lamin A such as LAP2a and BAF and to rescue histone H3K9 trimethylation. A recent paper by Das et al.3 clearly shows that even in animal models of progeria like the delta9/delta9 Lmna mouse, restoring H3K9 trimethylation is a key point to obtain rescue of the pathological phenotype. Further, it has been reported that rapamycin improves recruitment of DNA repair factors mimicking a situation observed in cells from long-lived subjects (Lattanzi et al., 2013).4 We are proud of giving a contribution through the European Journal of Histochemistry to the understanding of therapeutic approaches for the severe premature aging disease that affects Hutchinson-Gilford progeria patients. We thank you for allowing us to improve the quality and clearness of images in the Cenni’s 2011 paper, so that a better support to the available evidence of rapamycin efficacy in Hutchinson-Gilford progeria and related progeroid disorders may be offered. European Journal of Histochemistry 2013; volume 57:e42