Need for NAD+: Focus on Striated Muscle Laminopathies.

Déborah Cardoso,Antoine Muchir

doi:10.3390/cells9102248

Abstract

Laminopathies are a heterogeneous group of rare diseases caused by genetic mutations in the LMNA gene, encoding A-type lamins. A-type lamins are nuclear envelope proteins which associate with B-type lamins to form the nuclear lamina, a meshwork underlying the inner nuclear envelope of differentiated cells. The laminopathies include lipodystrophies, progeroid phenotypes and striated muscle diseases. Research on striated muscle laminopathies in the recent years has provided novel perspectives on the role of the nuclear lamina and has shed light on the pathological consequences of altered nuclear lamina. The role of altered nicotinamide adenine dinucleotide (NAD+) in the physiopathology of striated muscle laminopathies has been recently highlighted. Here, we have summarized these findings and reviewed the current knowledge about NAD+ alteration in striated muscle laminopathies, providing potential therapeutic approaches.

Highlights

Laminopathies are a heterogeneous group of genetic disorders caused by mutations in LMNA, which encodes nuclear A-type lamins: lamins A and C
This review focuses on the role played by NAD+ metabolism in striated muscles laminopathies, from bench to bedside
We recently demonstrated that the NAD+ content was significantly decreased in the heart of Lmnap.H222P/H222P mice, a model that recapitulates cardiomyopathy associated with

Summary

Introduction

Laminopathies are a heterogeneous group of genetic disorders caused by mutations in LMNA, which encodes nuclear A-type lamins: lamins A and C. Lamins A and C, which are members of the intermediate filaments family, dimerize and further assemble to form the nuclear lamina [2], a fibrillar meshwork contributing to cellular functions such as mechanotransduction, regulation of gene transcription and chromatin structure [3]. These intermediate filament proteins, the only intermediate filaments located within the nucleus, are expressed in most tissues. The discovery that several genetic diseases are caused by mutations in the LMNA gene has resulted in a reassessment of the function of the nuclear lamina

Laminopathies

Striated Muscle Laminopathies

Findings

Conclusions