title: A lysosomal lair for a pathogenic protein pair.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects movement. Although many of the causes of PD remain unclear, a consistent finding is the abnormal accumulation of the protein α-synuclein. In a recent issue of Cell, Mazzuli et al. provide a molecular explanation for the unexpected link between PD and Gaucher's disease, a glycolipid lysosomal storage disorder caused by loss of the enzyme glucocerebrosidase (GBA). They report a reciprocal connection between loss of GBA activity and the accumulation of α-synuclein in lysosomes that establishes a bidirectional positive feedback loop with pathogenic consequences. Understanding how lysosomes are implicated in PD may reveal new therapeutic targets for treating this disease.
authors.affiliation: Neuroregeneration Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. tdawson@jhmi.edu
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
authors.forename: Valina L
authors.initials: VL
authors.lastname: Dawson
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D005776:Gaucher Disease / Q000201:enzymology / Q000473:pathology / Q000628:therapy; D005962:Glucosylceramidase / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D005962:Glucosylceramidase