Seipinopathy: a novel endoplasmic reticulum stress-associated disease

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Seipinopathy: a novel endoplasmic reticulum stress-associated disease.

The Seipin/BSCL2 gene was originally identified as a loss-of-function gene for congenital generalized lipodystrophy type 2 (CGL2), a condition characterized by severe lipoatrophy, insulin resistance, hypertriglyceridaemia and mental retardation. Recently, gain-of-toxic-function mutations (namely, mutations N88S and S90L) in the seipin gene have been identified in autosomal dominant motor neuron...

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Endoplasmic Reticulum Stress and Associated ROS

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N88S seipin mutant transgenic mice develop features of seipinopathy/BSCL2-related motor neuron disease via endoplasmic reticulum stress.

Heterozygosity for mutations (N88S and P90L) in the N-glycosylation site of seipin/BSCL2 is associated with the autosomal dominant motor neuron diseases, spastic paraplegia 17 and distal hereditary motor neuropathy type V, referred to as 'seipinopathies'. Previous in vitro studies have shown that seipinopathy-linked mutations result in accumulation of unfolded proteins in the endoplasmic reticu...

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Unfolded proteins and other conditions affecting endoplasmic reticulum (ER) homeostasis cause ER stress. The cell reacts to ER stress by activation of the unfolded protein response (UPR), which induces profound changes in cellular metabolism including general translation attenuation, transcriptional upregulation of molecular chaperone genes, and activation of ER-associated degradation. However,...

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ژورنال

عنوان ژورنال: Brain

سال: 2008

ISSN: 1460-2156,0006-8950

DOI: 10.1093/brain/awn216