title: Glucocerebrosidase deficits in sporadic Parkinson disease.
abstract: Parkinson disease (PD) is a progressive neurodegenerative movement disorder characterized pathologically by abnormal SNCA/α-synuclein protein inclusions in neurons. Impaired lysosomal autophagic degradation of cellular proteins is implicated in PD pathogenesis and progression. Heterozygous GBA mutations, encoding lysosomal GBA/glucocerebrosidase (glucosidase, β, acid), are the greatest genetic risk factor for PD, and reduced GBA and SNCA accumulation are related in PD models. Here we review our recent human brain tissue study demonstrating that GBA deficits in sporadic PD are related to the early accumulation of SNCA, and dysregulation of chaperone-mediated autophagy (CMA) pathways and lipid metabolism.
authors.affiliation: Neuroscience Research Australia; School of Medical Sciences; Faculty of Medicine; University of New South Wales; Sydney, Australia.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Murphy
authors.affiliation: Neuroscience Research Australia; School of Medical Sciences; Faculty of Medicine; University of New South Wales; Sydney, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
mesh_terms: D001343:Autophagy; D005962:Glucosylceramidase / Q000172:deficiency*; D006801:Humans; D050356:Lipid Metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D010300:Parkinson Disease / Q000201:enzymology* / Q000473:pathology*; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; D051844:alpha-Synuclein; D005962:Glucosylceramidase
keywords: Parkinson disease; autophagy; ceramide; chaperone-mediated autophagy; glucocerebrosidase; lysosomes; α-synuclein