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

Abstract

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.

Abbreviations

ADLD:

adult-onset autosomal dominant leukodystrophy

APL:

acquired partial lipodystrophy

CMD1A:

dilated cardiomyopathy 1A with conduction defect

CMT2B1:

Charcot-Marie-Tooth disease type 2B1

DMD:

Duchenne muscular dystrophy

EDMD:

autosomal dominant Emery-Dreifuss muscular dystrophy

ERK:

extracellular signal-regulated kinase

GL:

generalized lipodystrophy

FPLD:

Dunnigan familial partial lipodystrophy

HGPS:

Hutchinson Gilford progeria syndrome

INM:

inner nuclear membrane

JNK:

c-Jun NH(2)-terminal kinase

LAP:

lamina-associated polypeptide

LBR:

p58 protein, lamin B receptor, 3 beta-hydroxysterol D14-reductase

LGMDB1:

limb-girdle muscular dystrophy type 1B

LINC:

linker of the nucleoskeleton and cytoskeleton

LMNA :

gene encoding A/C type lamins

MAD:

mandibuloacral dysplasia

NE:

nuclear envelope

PPARγ:

peroxisome proliferator-activated receptor γ

pRB:

retinoblastoma protein

ZMPSTE24/FACE1:

zinc metalloproteinase STE 24 homology

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Zaremba-Czogalla, M., Dubińska-Magiera, M. & Rzepecki, R. Laminopathies: The molecular background of the disease and the prospects for its treatment. Cell Mol Biol Lett 16, 114–148 (2011). https://doi.org/10.2478/s11658-010-0038-9

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Key words

  • Laminopathies
  • Nuclear lamina
  • Lamin
  • Emerin
  • Gene therapy