title: The Complicated Relationship between Gaucher Disease and Parkinsonism: Insights from a Rare Disease.
abstract: The discovery of a link between mutations in GBA1, encoding the lysosomal enzyme glucocerebrosidase, and the synucleinopathies directly resulted from the clinical recognition of patients with Gaucher disease with parkinsonism. Mutations in GBA1 are now the most common known genetic risk factor for several Lewy body disorders, and an inverse relationship exists between levels of glucocerebrosidase and oligomeric α-synuclein. While the underlying mechanisms are still debated, this complicated association is shedding light on the role of lysosomes in neurodegenerative disorders, demonstrating how insights from a rare disorder can direct research into the pathogenesis and therapy of seemingly unrelated common diseases.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3708, USA.
authors.forename: Elma
authors.initials: E
authors.lastname: Aflaki
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3708, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Westbroek
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3708, USA. Electronic address: sidranse@mail.nih.gov.
authors.forename: Ellen
authors.initials: E
authors.lastname: Sidransky
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005776:Gaucher Disease / Q000235:genetics*; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology; D035583:Rare Diseases / Q000235:genetics*
chemical_list: D005962:Glucosylceramidase
keywords: Gaucher disease; alpha-synuclein; autophagy; glucocerebrosidase; lysosome; parkinsonism