期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1792, 期 9, 页码 881-887出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2009.07.001
关键词
Muscular dystrophy; Sialic acid synthesis; UDP-GlcNAc 2-epimerase/ManNAc kinase; Hyposialylation; HIBM mouse model; ManNAc therapy; GNE mutation
资金
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive. quadriceps sparing type commonly referred to as HIBM but also termed h-IBM or Inclusion Body Myopathy 2 (IBM2). The clinical manifestations begin with muscle weakness progressing over the next 10-20 years uniquely sparing the quadriceps until the most advanced stage of the disease. Histopathology of an HIBM muscle biopsy shows rimmed vacuoles on Comori's trichrome stain, small fibers in groups and tubulofilaments without evidence of inflammation. In affected individuals distinct mutations have been identified in the GNE gene, which encodes the bifunctional enzyme uridine diphospho-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase/N-acetyl-mannosamine (ManNAc) kinase (GNE/MNK). GNE/MNK catalyzes the first two committed steps in the biosynthesis of acetylneuraminic acid (Neu5Ac), an abundant and functionally important sugar. The generation of HIBM animal models has led to novel insights into both the disease and the role of GNE/MNK in pathophysiology. Recent advances in therapeutic approaches for HIBM, including administration of N-acetyl-mannosamine (ManNAc), a precursor of Neu5Ac will be discussed. Published by Elsevier B.V.
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