Laminopathies

Abstract

The laminopathies are a group of rare diseases characterized by a vast range of phenotypic alterations, due to mutations in lamin A and C or other nuclear envelope proteins. A-type lamins, as well as B-type lamins, belong to the type V intermediate filaments and, by polymerization, form the nuclear lamina, a component of the nuclear envelope. Following a brief description of the complex interactions between lamins and proteins of the nuclear membrane, this Chapter describes disease phenotypes that characterize each laminopathy, the possible mechanisms involved into the pathogenesis, as well as potential therapies based on the use of existing drugs. IntroductionFor many years, the nuclear lamina has been considered a structural component of the nuclear envelope (NE, [1]) and has been studied by cell biologists working on the description of the different phases of mitosis [2]. After the discovery that mutations in the genes encoding A-type lamins and associated NE proteins cause an impressive range of human diseases [3], new and unexpected functions have been attributed to lamins and the interest in the nuclear lamina has been greatly enhanced. Here, a description of the nuclear lamina intermediate filament network and of laminlinked diseases known as "laminopathies" will be provided. Although a detailed description of the NE is outside the scope of this Chapter, a brief overview of the general organization of this nuclear domain, with references to recent reviews on the subject will be presented in order to help the comprehension of disease mechanisms.As schematically indicated in Fig. 18.1, in the NE the outer and inner nuclear membranes ONM and INM) are not equivalent; in fact, the ONM is continuous N. M. Maraldi ( )