Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
6.0
Journals
Cells
Special Issues
The New Frontier of Therapies for Nuclear Envelope and Lamin-Related...
share announcement

The New Frontier of Therapies for Nuclear Envelope and Lamin-Related Diseases: Selected Papers from 2019 International Meeting on Laminopathies

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 31741

Special Issue Editors

Dr. Giovanna Lattanzi

E-Mail Website
Guest Editor
CNR Institute of Molecular Genetics, Unit of Bologna, Bologna, Italy
Interests: laminopathies; cell biology of lamins, emerin- and lamin-linked proteins; Emery-Dreifuss muscular dystrophy; Hutchinson–Gilford progeria syndrome (HGPS); mandibuloacral dysplasia; familial partial lipodystrophy type 2
Dr. Thomas Dechat

E-Mail Website
Guest Editor
Ludwig Boltzmann Institute of Osteology, 1st Medical Department of Hanusch Hospital, Heinrich Collin Str. 30, A-1140 Vienna, Austria
Interests: nuclear lamins; LAP2alpha; nuclear structure; nuclear envelope disassembly and assembly; chromatin organization; cell cycle regulation; premature aging; osteogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will consist of selected papers from the 2019 International Meeting on Laminopathies on 2–5 September 2019 in London, UK. This is the 3rd edition of the International Meeting on Laminopathies, which is organized every other year in diverse European countries to gather scientists, clinicians, and patient organizations dealing with lamin research and laminopathies. This event is organized by the Italian Network for Laminopathies and by the French Network for Emery-Dreifuss muscular dystrophy and other nuclear envelope-related diseases. Previous meetings took place in Marseille (France) in 2015 and Bologna (Italy) in 2017. The 2019 edition has been organized as a joint meeting with the UK Nuclear Envelope and Chromatin Organization Meeting, organized by Qiuping Zhang and Kathy Shanahan at King’s College in London in collaboration with Eric Schirmer from the University of Edinburgh. Moreover, a satellite meeting of the European Network for Laminopathies has been scheduled on 3–5 September 2019 to allow cross-fertilization among European researchers, clinicians, patients, and their associations and to foster collaborations. This Special Issue of Cells will be focused on “The New Frontier of Therapies for Nuclear Envelope- and Lamin-Related Diseases”.

In this Special Issue, we aim to highlight approaches that exploit experimental work to identify therapeutic targets and test new therapeutic strategies, which we hope can provide a cure for laminopathies. This Special Issue thus offers the opportunity for attendees of the meeting to contribute and publish research findings and perspectives in this area.

Selected papers from the 2019 International Meeting on Laminopathies reporting on “The New Frontier of Therapies for Nuclear Envelope- and Lamin-Related Diseases” will be considered for publication. The papers submitted and selected for this Special Issue should neither have been previously published nor be under consideration for publication elsewhere and will be subject to a very rigorous peer-review process.

Dr. Giovanna Lattanzi
Dr. Thomas Dechat
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lamin
  • nuclear envelope
  • laminopathies
  • therapies for laminopathies

Related Special Issue

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

22 pages, 9206 KiB  
Article
Impact of Progerin Expression on Adipogenesis in Hutchinson—Gilford Progeria Skin-Derived Precursor Cells
by Farah Najdi, Peter Krüger and Karima Djabali
Cells 2021, 10(7), 1598; https://doi.org/10.3390/cells10071598 - 25 Jun 2021
Cited by 7 | Viewed by 4634
Abstract
Hutchinson–Gilford progeria syndrome (HGPS) is a segmental premature aging disease caused by a mutation in LMNA. The mutation generates a truncated and farnesylated form of prelamin A, called progerin. Affected individuals develop several features of normal aging, including lipodystrophy caused by the [...] Read more.
Hutchinson–Gilford progeria syndrome (HGPS) is a segmental premature aging disease caused by a mutation in LMNA. The mutation generates a truncated and farnesylated form of prelamin A, called progerin. Affected individuals develop several features of normal aging, including lipodystrophy caused by the loss of general subcutaneous fat. To determine whether premature cellular senescence is responsible for the altered adipogenesis in patients with HGPS, we evaluated the differentiation of HGPS skin-derived precursor stem cells (SKPs) into adipocytes. The SKPs were isolated from primary human HGPS and normal fibroblast cultures, with senescence of 5 and 30%. We observed that the presence of high numbers of senescent cells reduced SKPs’ adipogenic differentiation potential. Treatment with baricitinib, a JAK–STAT inhibitor, ameliorated the ability of HGPS SKPs to differentiate into adipocytes. Our findings suggest that the development of lipodystrophy in patients with HGPS may be associated with an increased rate of cellular senescence and chronic inflammation. Full article
(This article belongs to the Special Issue The New Frontier of Therapies for Nuclear Envelope and Lamin-Related Diseases: Selected Papers from 2019 International Meeting on Laminopathies)
►▼ Show Figures

Graphical abstract

21 pages, 6129 KiB  
Article
Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells during Replicative Senescence
by Jennifer M. Röhrl, Rouven Arnold and Karima Djabali
Cells 2021, 10(1), 153; https://doi.org/10.3390/cells10010153 - 14 Jan 2021
Cited by 14 | Viewed by 4465
Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease caused by a mutation in LMNA. A G608G mutation in exon 11 of LMNA is responsible for most HGPS cases, generating a truncated protein called “progerin”. Progerin is permanently farnesylated and accumulates [...] Read more.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease caused by a mutation in LMNA. A G608G mutation in exon 11 of LMNA is responsible for most HGPS cases, generating a truncated protein called “progerin”. Progerin is permanently farnesylated and accumulates in HGPS cells, causing multiple cellular defects such as nuclear dysmorphism, a thickened lamina, loss of heterochromatin, premature senescence, and clustering of Nuclear Pore Complexes (NPC). To identify the mechanism of NPC clustering in HGPS cells, we evaluated post-mitotic NPC assembly in control and HGPS cells and found no defects. Next, we examined the occurrence of NPC clustering in control and HGPS cells during replicative senescence. We reported that NPC clustering occurs solely in the dysmorphic nuclei of control and HGPS cells. Hence, NPC clustering occurred at a higher frequency in HGPS cells compared to control cells at early passages; however, in late cultures with similar senescence index, NPCs clustering occurred at a similar rate in both control and HGPS. Our results show that progerin does not disrupt post-mitotic reassembly of NPCs. However, NPCs frequently cluster in dysmorphic nuclei with a high progerin content. Additionally, nuclear envelope defects that arise during replicative senescence cause NPC clustering in senescent cells with dysmorphic nuclei. Full article
(This article belongs to the Special Issue The New Frontier of Therapies for Nuclear Envelope and Lamin-Related Diseases: Selected Papers from 2019 International Meeting on Laminopathies)
►▼ Show Figures

Graphical abstract

19 pages, 9395 KiB  
Article
Premature Vascular Aging with Features of Plaque Vulnerability in an Atheroprone Mouse Model of Hutchinson–Gilford Progeria Syndrome with Ldlr Deficiency
by Rosa M. Nevado, Magda R. Hamczyk, Pilar Gonzalo, María Jesús Andrés-Manzano and Vicente Andrés
Cells 2020, 9(10), 2252; https://doi.org/10.3390/cells9102252 - 08 Oct 2020
Cited by 13 | Viewed by 3123
Abstract
Hutchinson–Gilford progeria syndrome (HGPS) is among the most devastating of the laminopathies, rare genetic diseases caused by mutations in genes encoding nuclear lamina proteins. HGPS patients age prematurely and die in adolescence, typically of atherosclerosis-associated complications. The mechanisms of HGPS-related atherosclerosis are not [...] Read more.
Hutchinson–Gilford progeria syndrome (HGPS) is among the most devastating of the laminopathies, rare genetic diseases caused by mutations in genes encoding nuclear lamina proteins. HGPS patients age prematurely and die in adolescence, typically of atherosclerosis-associated complications. The mechanisms of HGPS-related atherosclerosis are not fully understood due to the scarcity of patient-derived samples and the availability of only one atheroprone mouse model of the disease. Here, we generated a new atherosusceptible model of HGPS by crossing progeroid LmnaG609G/G609G mice, which carry a disease-causing mutation in the Lmna gene, with Ldlr−/− mice, a commonly used preclinical atherosclerosis model. Ldlr−/−LmnaG609G/G609G mice aged prematurely and had reduced body weight and survival. Compared with control mice, Ldlr−/−LmnaG609G/G609G mouse aortas showed a higher atherosclerosis burden and structural abnormalities typical of HGPS patients, including vascular smooth muscle cell depletion in the media, adventitial thickening, and elastin structure alterations. Atheromas of Ldlr−/−LmnaG609G/G609G mice had features of unstable plaques, including the presence of erythrocytes and iron deposits and reduced smooth muscle cell and collagen content. Ldlr−/−LmnaG609G/G609G mice faithfully recapitulate vascular features found in patients and thus provide a new tool for studying the mechanisms of HGPS-related atherosclerosis and for testing therapies. Full article
(This article belongs to the Special Issue The New Frontier of Therapies for Nuclear Envelope and Lamin-Related Diseases: Selected Papers from 2019 International Meeting on Laminopathies)
►▼ Show Figures

Graphical abstract

15 pages, 5200 KiB  
Article
PCAF Involvement in Lamin A/C-HDAC2 Interplay during the Early Phase of Muscle Differentiation
by Spartaco Santi, Vittoria Cenni, Cristina Capanni, Giovanna Lattanzi and Elisabetta Mattioli
Cells 2020, 9(7), 1735; https://doi.org/10.3390/cells9071735 - 20 Jul 2020
Cited by 12 | Viewed by 3462
Abstract
Lamin A/C has been implicated in the epigenetic regulation of muscle gene expression through dynamic interaction with chromatin domains and epigenetic enzymes. We previously showed that lamin A/C interacts with histone deacetylase 2 (HDAC2). In this study, we deepened the relevance and regulation [...] Read more.
Lamin A/C has been implicated in the epigenetic regulation of muscle gene expression through dynamic interaction with chromatin domains and epigenetic enzymes. We previously showed that lamin A/C interacts with histone deacetylase 2 (HDAC2). In this study, we deepened the relevance and regulation of lamin A/C-HDAC2 interaction in human muscle cells. We present evidence that HDAC2 binding to lamin A/C is related to HDAC2 acetylation on lysine 75 and expression of p300-CBP associated factor (PCAF), an acetyltransferase known to acetylate HDAC2. Our findings show that lamin A and farnesylated prelamin A promote PCAF recruitment to the nuclear lamina and lamin A/C binding in human myoblasts committed to myogenic differentiation, while protein interaction is decreased in differentiating myotubes. Interestingly, PCAF translocation to the nuclear envelope, as well as lamin A/C-PCAF interaction, are reduced by transient expression of lamin A mutated forms causing Emery Dreifuss muscular dystrophy. Consistent with this observation, lamin A/C interaction with both PCAF and HDAC2 is significantly reduced in Emery–Dreifuss muscular dystrophy myoblasts. Overall, these results support the view that, by recruiting PCAF and HDAC2 in a molecular platform, lamin A/C might contribute to regulate their epigenetic activity required in the early phase of muscle differentiation. Full article
(This article belongs to the Special Issue The New Frontier of Therapies for Nuclear Envelope and Lamin-Related Diseases: Selected Papers from 2019 International Meeting on Laminopathies)
►▼ Show Figures

Figure 1

21 pages, 5307 KiB  
Article
Consequences of Lmna Exon 4 Mutations in Myoblast Function
by Déborah Gómez-Domínguez, Carolina Epifano, Fernando de Miguel, Albert García Castaño, Borja Vilaplana-Martí, Alberto Martín, Sandra Amarilla-Quintana, Anne T Bertrand, Gisèle Bonne, Javier Ramón-Azcón, Miguel A Rodríguez-Milla and Ignacio Pérez de Castro
Cells 2020, 9(5), 1286; https://doi.org/10.3390/cells9051286 - 21 May 2020
Cited by 5 | Viewed by 7356
Abstract
Laminopathies are causally associated with mutations on the Lamin A/C gene (LMNA). To date, more than 400 mutations in LMNA have been reported in patients. These mutations are widely distributed throughout the entire gene and are associated with a wide range [...] Read more.
Laminopathies are causally associated with mutations on the Lamin A/C gene (LMNA). To date, more than 400 mutations in LMNA have been reported in patients. These mutations are widely distributed throughout the entire gene and are associated with a wide range of phenotypes. Unfortunately, little is known about the mechanisms underlying the effect of the majority of these mutations. This is the case of more than 40 mutations that are located at exon 4. Using CRISPR/Cas9 technology, we generated a collection of Lmna exon 4 mutants in mouse C2C12 myoblasts. These cell models included different types of exon 4 deletions and the presence of R249W mutation, one of the human variants associated with a severe type of laminopathy, LMNA-associated congenital muscular dystrophy (L-CMD). We characterized these clones by measuring their nuclear circularity, myogenic differentiation capacity in 2D and 3D conditions, DNA damage, and levels of p-ERK and p-AKT (phosphorylated Mitogen-Activated Protein Kinase 1/3 and AKT serine/threonine kinase 1). Our results indicated that Lmna exon 4 mutants showed abnormal nuclear morphology. In addition, levels and/or subcellular localization of different members of the lamin and LINC (LInker of Nucleoskeleton and Cytoskeleton) complex were altered in all these mutants. Whereas no significant differences were observed for ERK and AKT activities, the accumulation of DNA damage was associated to the Lmna p.R249W mutant myoblasts. Finally, significant myogenic differentiation defects were detected in the Lmna exon 4 mutants. These results have key implications in the development of future therapeutic strategies for the treatment of laminopathies. Full article
(This article belongs to the Special Issue The New Frontier of Therapies for Nuclear Envelope and Lamin-Related Diseases: Selected Papers from 2019 International Meeting on Laminopathies)
►▼ Show Figures

Figure 1

17 pages, 2647 KiB  
Article
Lamin A/C Assembly Defects in LMNA-Congenital Muscular Dystrophy Is Responsible for the Increased Severity of the Disease Compared with Emery–Dreifuss Muscular Dystrophy
by Anne T. Bertrand, Astrid Brull, Feriel Azibani, Louise Benarroch, Khadija Chikhaoui, Colin L. Stewart, Ohad Medalia, Rabah Ben Yaou and Gisèle Bonne
Cells 2020, 9(4), 844; https://doi.org/10.3390/cells9040844 - 31 Mar 2020
Cited by 24 | Viewed by 4940
Abstract
LMNA encodes for Lamin A/C, type V intermediate filaments that polymerize under the inner nuclear membrane to form the nuclear lamina. A small fraction of Lamin A/C, less polymerized, is also found in the nucleoplasm. Lamin A/C functions include roles in nuclear resistance [...] Read more.
LMNA encodes for Lamin A/C, type V intermediate filaments that polymerize under the inner nuclear membrane to form the nuclear lamina. A small fraction of Lamin A/C, less polymerized, is also found in the nucleoplasm. Lamin A/C functions include roles in nuclear resistance to mechanical stress and gene regulation. LMNA mutations are responsible for a wide variety of pathologies, including Emery–Dreifuss (EDMD) and LMNA-related congenital muscular dystrophies (L-CMD) without clear genotype–phenotype correlations. Both diseases presented with striated muscle disorders although L-CMD symptoms appear much earlier and are more severe. Seeking for pathomechanical differences to explain the severity of L-CMD mutations, we performed an in silico analysis of the UMD-LMNA database and found that L-CMD mutations mainly affect residues involved in Lamin dimer and tetramer stability. In line with this, we found increased nucleoplasmic Lamin A/C in L-CMD patient fibroblasts and mouse myoblasts compared to the control and EDMD. L-CMD myoblasts show differentiation defects linked to their inability to upregulate muscle specific nuclear envelope (NE) proteins expression. NE proteins were mislocalized, leading to misshapen nuclei. We conclude that these defects are due to both the absence of Lamin A/C from the nuclear lamina and its maintenance in the nucleoplasm of myotubes. Full article
(This article belongs to the Special Issue The New Frontier of Therapies for Nuclear Envelope and Lamin-Related Diseases: Selected Papers from 2019 International Meeting on Laminopathies)
►▼ Show Figures

Figure 1

14 pages, 2802 KiB  
Article
Looking at New Unexpected Disease Targets in LMNA-Linked Lipodystrophies in the Light of Complex Cardiovascular Phenotypes: Implications for Clinical Practice
by Héléna Mosbah, Camille Vatier, Franck Boccara, Isabelle Jéru, Olivier Lascols, Marie-Christine Vantyghem, Bruno Fève, Bruno Donadille, Elisabeth Sarrazin, Sophie Benabbou, Jocelyn Inamo, Stéphane Ederhy, Ariel Cohen, Barbara Neraud, Pascale Richard, Fabien Picard, Sophie Christin-Maitre, Alban Redheuil, Karim Wahbi and Corinne Vigouroux
Cells 2020, 9(3), 765; https://doi.org/10.3390/cells9030765 - 20 Mar 2020
Cited by 9 | Viewed by 2740
Abstract
Variants in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and progeroid syndromes. Cardiovascular laminopathic involvement is classically described as cardiomyopathy in striated muscle laminopathies, and arterial wall dysfunction and/or valvulopathy in lipodystrophic and/or progeroid laminopathies. We report [...] Read more.
Variants in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and progeroid syndromes. Cardiovascular laminopathic involvement is classically described as cardiomyopathy in striated muscle laminopathies, and arterial wall dysfunction and/or valvulopathy in lipodystrophic and/or progeroid laminopathies. We report unexpected cardiovascular phenotypes in patients with LMNA-associated lipodystrophies, illustrating the complex multitissular pathophysiology of the disease and the need for specific cardiovascular investigations in affected patients. A 33-year-old woman was diagnosed with generalized lipodystrophy and atypical progeroid syndrome due to the newly identified heterozygous LMNA p.(Asp136Val) variant. Her complex cardiovascular phenotype was associated with atherosclerosis, aortic valvular disease and left ventricular hypertrophy with rhythm and conduction defects. A 29-year-old woman presented with a partial lipodystrophy syndrome and a severe coronary atherosclerosis which required a triple coronary artery bypass grafting. She carried the novel heterozygous p.(Arg60Pro) LMNA variant inherited from her mother, affected with partial lipodystrophy and dilated cardiomyopathy. Different lipodystrophy-associated LMNA pathogenic variants could target cardiac vasculature and/or muscle, leading to complex overlapping phenotypes. Unifying pathophysiological hypotheses should be explored in several cell models including adipocytes, cardiomyocytes and vascular cells. Patients with LMNA-associated lipodystrophy should be systematically investigated with 24-h ECG monitoring, echocardiography and non-invasive coronary function testing. Full article
(This article belongs to the Special Issue The New Frontier of Therapies for Nuclear Envelope and Lamin-Related Diseases: Selected Papers from 2019 International Meeting on Laminopathies)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop