Premium
Gaucher disease paradigm: From ERAD to comorbidity
Author(s) -
BendikovBar Inna,
Horowitz Mia
Publication year - 2012
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22124
Subject(s) - endoplasmic reticulum associated protein degradation , endoplasmic reticulum , glucocerebrosidase , biology , mutant , unfolded protein response , proteasome , gene , mutation , microbiology and biotechnology , genetics
Mutations in the GBA gene, encoding the lysosomal acid beta‐glucocerebrosidase (GCase), lead to deficient activity of the enzyme in the lysosomes, to glucosylceramide accumulation and to development of Gaucher disease (GD). More than 280 mutations in the GBA gene have been directly associated with GD. Mutant GCase variants present variable levels of endoplasmic reticulum (ER) retention, due to their inability to correctly fold, and undergo ER‐associated degradation (ERAD) in the proteasomes. The degree of ER retention and proteasomal degradation is one of the factors that determine GD severity. In the present review, we discuss ERAD of mutant GCase variants and its possible consequences in GD patients and in carriers of GD mutations. Hum Mutat 33:1398–1407, 2012. © 2012 Wiley Periodicals, Inc.