New Directions in Gaucher Disease

Mia Horowitz*, Deborah Elstein, Ari Zimran, Ozlem Goker-Alpan

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


In Gaucher disease (GD), mutant lysosomal acid β-glucocerebrosidase fails to properly hydrolyze its substrate, glucosylceramide, which accumulates in the lysosomes. Due to its phenotypic heterogeneity, GD has been classified into type 1, non-neuronopathic, and types 2 and 3, the neuronopathic forms, based on the primary involvement of the central nervous system. Neuroinflammation and necroptotic death may appear in the neuronopathic forms of GD, whereas type 1 GD patients may develop Parkinson disease (PD), a prototype of protein misfolding disorders of the nervous system. PD is significantly more prevalent among GD carriers and patients than among the non-GD populations. It is apparent that the amount of mutant enzyme present in lysosomes depends on the amount of mutant enzyme recognized as correctly folded in the endoplasmic reticulum (ER) for physiologically correct transport through the Golgi apparatus to the lysosome. Mutant enzyme recognized as misfolded is retained in the ER, inducing the Unfolded Protein Response. In the current review, we present three discrete areas of interest: molecular and cellular mechanisms underlying the association between GD and PD; the clinical and genetic associations between GD and PD; and treatment options for GD. We also discuss the relevance of induced pleuripotent stem cells to the above associations.

Original languageEnglish
Pages (from-to)1121-1136
Number of pages16
JournalHuman Mutation
Issue number11
StatePublished - 1 Nov 2016


FundersFunder number
Teva Pharmaceutical Industries
Sanofi Genzyme
Israel Science Foundation


    • Gaucher disease
    • Parkinson disease
    • Unfolded Protein Response
    • glucocerebrosidase
    • induced pleuripotent stem cells


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