title: Reduced expression of the chaperone-mediated autophagy carrier hsc70 protein in lymphomonocytes of patients with Parkinson's disease.
abstract: Chaperone-mediated autophagy (CMA) impairment is recognized to play a pathogenetic role in Parkinson's disease (PD). A reduced expression of lysosomal-associated membrane protein (lamp) 2A and heat shock cognate (hsc) 70 protein, the two key regulators of CMA, has been reported in brains of PD patients. To verify the existence of a possible systemic CMA dysfunction in PD, in this study the expression of hsc70 and lamp2A was assessed in peripheral blood mononuclear cells (PBMC) of patients with sporadic PD and compared to healthy subjects. The expression of myocyte enhancer factor 2D (MEF2D), a transcriptional factor implicated in neuronal survival and specific substrate of CMA, was also evaluated. Protein and gene expression was assessed by Western blot and real-time PCR, respectively, in PBMC obtained from 53 sporadic PD patients and 53 healthy subjects. A significant reduction of hsc70 levels was observed in PBMC of PD patients, both under basal conditions and after autophagy induction obtained with serum deprivation. No difference emerged in lamp2A and MEF2D expression between patients and controls. No influence of the clinical characteristics of patients emerged on hsc70, lamp2A and MEF2D expression. These results, despite being not suggestive of the existence of a CMA impairment in PBMC of PD patients, identify a systemic hsc70 reduction in PD patients. Further studies on specific mechanisms and biological significance of such alteration are needed to corroborate this finding that could lead to the identification of a new trait biomarker for PD.
authors.affiliation: Laboratory of Neurobiology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy. Electronic address: gessica.sala@unimib.it.
authors.forename: Gessica
authors.initials: G
authors.lastname: Sala
authors.affiliation: Laboratory of Neurobiology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy; Department of Neurology, San Gerardo Hospital, Monza, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stefanoni
authors.affiliation: Laboratory of Neurobiology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy; PhD program in Neuroscience, University of Milano-Bicocca, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Arosio
authors.affiliation: Laboratory of Neurobiology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Riva
authors.affiliation: Laboratory of Neurobiology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Melchionda
authors.affiliation: Laboratory of Neurobiology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy; Department of Neurology, San Gerardo Hospital, Monza, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Saracchi
authors.affiliation: Laboratory of Neurobiology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy; Department of Neurology, San Gerardo Hospital, Monza, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fermi
authors.affiliation: Department of Neurology, San Gerardo Hospital, Monza, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Brighina
authors.affiliation: Laboratory of Neurobiology, Department of Surgery and Translational Medicine, University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy; Department of Neurology, San Gerardo Hospital, Monza, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrarese
mesh_terms: D000368:Aged; D001343:Autophagy / Q000502:physiology*; D002470:Cell Survival; D005260:Female; D050883:HSC70 Heat-Shock Proteins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D052119:Lysosomal-Associated Membrane Protein 2 / Q000097:blood / Q000378:metabolism; D064326:MEF2 Transcription Factors / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000378:metabolism*
chemical_list: D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D064326:MEF2 Transcription Factors; C578043:MEF2D protein, human
keywords: Chaperone-mediated autophagy; Hsc70; Lamp2a; MEF2D; Parkinson's disease; Peripheral blood mononuclear cell