Mechanisms of Gaucher disease pathogenesis.

摘要: Gaucher disease is caused by mutations in the Gba1 gene encoding an acid β-glucocerebrosidase (GBA1), lysosomal hydrolase which breaks down glucosylceramide (GlcCer). In type 1 accumulation of this simple glycolipid mainly restricted to tissue phagocyte lysosomes resulting ultimately hepatomegaly, splenomegaly and osteopenia. Lower residual GBA1 levels leads neuronal storage, types 2 3 neurological symptoms are characterised acute (death at age 2) or sub-acute onset, respectively. The links between cellular changes clinical manifestations largely unknown but key development monitoring new therapies. newcomer likely attracted apparent simplicity autosomal recessive disorder promises unravel critical GlcCer function normal cells (GlcCer widespread, it’s even present some bacteria—also, mouse fly knockouts die embryo stage). However, closer acquaintance reveals not a classic Mendelian disorder—sometimes monozygotic twins have different symptoms—and studies level so far failed reveal clear functions. Now team led Ellen Sidransky NIH has taken what appears be big step forward producing two vitro models (1).