title: Lysosomal alterations in peripheral blood mononuclear cells of Parkinson's disease patients.
abstract: BACKGROUND
  Reduced expression of lysosomal-associated membrane protein 2a and heatshock-cognate 70 proteins, involved in chaperone-mediated autophagy and of glucocerebrosidase, is reported in PD brains. The aim of this study was to identify systemic alterations in lysosomal-associated membrane protein 2a, heatshock cognate-70, and glucocerebrosidase levels/activity in peripheral blood mononuclear cells from PD patients.
  
  
  METHODS
  Protein/mRNA levels were assessed in PD patients from genetically undetermined background, alpha-synuclein (G209A/A53T), or glucocerebrosidase mutation carriers and age-/sex-matched controls.
  
  
  RESULTS
  Heatshock cognate 70 protein levels were reduced in all PD groups, whereas its mRNA levels were decreased only in the genetically undetermined group. Glucocerebrosidase protein levels were decreased only in the genetic PD groups, whereas increased mRNA levels and decreased activity were detected only in the glucocerebrosidase mutation group.
  
  
  CONCLUSIONS
  Reduced heatshock cognate-70 levels are suggestive of an apparent systemic chaperone-mediated autophagy dysfunction irrespective of genetic background. Glucocerebrosidase activity may serve as a screening tool to identify glucocerebrosidase mutation carriers with PD.
authors.affiliation: Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.|Second Department of Neurology, University of Athens Medical School, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papagiannakis
authors.affiliation: Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Xilouri
authors.affiliation: Second Department of Neurology, University of Athens Medical School, Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Koros
authors.affiliation: Second Department of Neurology, University of Athens Medical School, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Stamelou
authors.affiliation: Second Department of Neurology, University of Athens Medical School, Athens, Greece.
authors.forename: Roubina
authors.initials: R
authors.lastname: Antonelou
authors.affiliation: Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Matina
authors.initials: M
authors.lastname: Maniati
authors.affiliation: Dynan Hospital, Athens, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Papadimitriou
authors.affiliation: Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Moraitou
authors.affiliation: Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Michelakakis
authors.affiliation: Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.|Second Department of Neurology, University of Athens Medical School, Athens, Greece.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Stefanis
mesh_terms: D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005962:Glucosylceramidase / Q000235:genetics / Q000378:metabolism; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
chemical_list: D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D051907:Lysosomal Membrane Proteins; D012333:RNA, Messenger; D051844:alpha-Synuclein; D005962:Glucosylceramidase
keywords: Hsc70; Parkinson's disease; alpha-synuclein; chaperone-mediated autophagy (CMA); glucocerebrosidase (GCase); lysosome