141st ENMC International Workshop Inaugural Meeting of the EURO-Laminopathies Project Nuclear Envelope-linked Rare Human Diseases: From Molecular Pathophysiology towards Clinical Applications 10–12 March 2006, Naarden, The Netherlands (original) (raw)

Advances in basic and clinical research in laminopathies

Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases, 2013

Lamins (LMNA) are the main proteins of the nuclear lamina considered to be the ancestors of all intermediate filament proteins. They form complex protein assemblies with integral proteins of the inner nuclear membrane, transcriptional regulators, histones and chromatin modifiers. During recent years, interest in lamins has greatly increased due to the identification of many distinct heritable human disorders associated with lamin mutations. These disorders, collectively termed laminopathies, range from muscular dystrophies to premature aging. They may affect muscle, fat, bone, nerve and skin tissues. The workshop was addressed to understand lamin organization and its roles in nuclear processes, mutations in lamins affecting cell and tissues functions, the biology of the nucleus and laminopathic disease mechanisms, all aspects important for designing future therapies.

“Laminopathies”: A wide spectrum of human diseases

Experimental Cell Research, 2007

Mutations in genes encoding the intermediate filament nuclear lamins and associated proteins cause a wide spectrum of diseases sometimes called "laminopathies." Diseases caused by mutations in LMNA encoding A-type lamins include autosomal dominant Emery-Dreifuss muscular dystrophy and related myopathies, Dunnigan-type familial partial lipodystrophy, Charcot-Marie-Tooth disease type 2B1 and developmental and accelerated aging disorders. Duplication in LMNB1 encoding lamin B1 causes autosomal dominant leukodystrophy and mutations in LMNB2 encoding lamin B2 are associated with acquired partial lipodystrophy. Disorders caused by mutations in genes encoding lamin-associated integral inner nuclear membrane proteins include X-linked Emery-Dreifuss muscular dystrophy, sclerosing bone dysplasias, HEM/Greenberg skeletal dysplasia and Pelger-Huet anomaly. While mutations and clinical phenotypes of "laminopathies" have been carefully described, data explaining pathogenic mechanisms are only emerging. Future investigations will likely identify new "laminopathies" and a combination of basic and clinical research will lead to a better understanding of pathophysiology and the development of therapies.

Laminopathies: The molecular background of the disease and the prospects for its treatment

Cellular & Molecular Biology Letters, 2011

Laminopathies are rare human degenerative disorders with a wide spectrum of clinical phenotypes, associated with defects in the main protein components of the nuclear envelope, mostly in the lamins. They include systemic disorders and tissue-restricted diseases. Scientists have been trying to explain the pathogenesis of laminopathies and find an efficient method for treatment for many years. In this review, we discuss the current state of knowledge about laminopathies, the molecular mechanisms behind the development of particular phenotypes, and the prospects for stem cell and/or gene therapy treatments.

Emerging perspectives on laminopathies

Cell Health and Cytoskeleton, 2016

Laminopathies are a group of inherited disorders caused by mutations in the lamin A/C gene, and can affect diverse organs or tissues, or can be systemic, causing premature aging. In the present review, we report on the composition and structure of the nuclear lamina and the role of lamins in nuclear mechanics and their involvement in human diseases, and provide some examples of laminopathies and current therapeutic approaches.

Laminopathies and lamin-associated signaling pathways

Journal of Cellular Biochemistry, 2011

Laminopathies are genetic diseases due to mutations or altered post-translational processing of nuclear envelope/lamina proteins. The majority of laminopathies are caused by mutations in the LMNA gene, encoding lamin A/C, but manifest as diverse pathologies including muscular dystrophy, lipodystrophy, neuropathy, and progeroid syndromes. Lamin-binding proteins implicated in laminopathies include lamin B2, nuclear envelope proteins such as emerin, MAN1, LBR, and nesprins, the nuclear matrix protein matrin 3, the lamina-associated polypeptide, LAP2alpha and the transcriptional regulator FHL1. Thus, the altered functionality of a nuclear proteins network appears to be involved in the onset of laminopathic diseases. The functional interplay among different proteins involved in this network implies signaling partners. The signaling effectors may either modify nuclear envelope proteins and their binding properties, or use nuclear envelope/lamina proteins as platforms to regulate signal transduction. In this review, both aspects of lamin-linked signaling are presented and the major pathways so far implicated in laminopathies are summarized.

1 . 3 Novel Therapeutic Approaches , Proofs of Principle in Laminopathies

2015

I1 An overview of new translational, clinical and therapeutic perspectives in laminopathies and other nuclear envelope-related diseases Annachiara De Sandre-Giovannoli, Nicolas Levy, Rabah Ben Yaou, France Leturcq, Giovanna Lattanzi, Gisèle Bonne Aix Marseille Université, INSERM, GMGF UMR_S 910 & Department of Medical Genetics and Cell Biology, La Timone Children’s hospital, APHM, 13385, Marseille, France; Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, F-75013 Paris, France; Institut de Myologie, F-75013, Paris, France; AP-HP, Groupe Hospitalier Cochin-Broca-Hôtel Dieu, Laboratoire de biochimie et génétique moléculaire, Paris, France; CNR Institute for Molecular Genetics, Unit of Bologna, Bologna, Italy; Rizzoli Orthopedic Institute, Laboratory of Musculoskeletal Cell Biology, Bologna, Italy E-mail: g.bonne@institut-myologie.org Orphanet Journal of Rare Diseases 2015, 10(Suppl 2):I1