PMID- 24361989
OWN - NLM
STAT- MEDLINE
DCOM- 20140908
LR  - 20140120
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1546
DP  - 2014 Feb 10
TI  - Reduced expression of the chaperone-mediated autophagy carrier hsc70 protein in 
      lymphomonocytes of patients with Parkinson's disease.
PG  - 46-52
LID - S0006-8993(13)01564-3 [pii]
LID - 10.1016/j.brainres.2013.12.017 [doi]
AB  - 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.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Sala, Gessica
AU  - Sala G
AD  - 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.
FAU - Stefanoni, Giovanni
AU  - Stefanoni G
AD  - 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.
FAU - Arosio, Alessandro
AU  - Arosio A
AD  - 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.
FAU - Riva, Chiara
AU  - Riva C
AD  - Laboratory of Neurobiology, Department of Surgery and Translational Medicine, 
      University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
FAU - Melchionda, Laura
AU  - Melchionda L
AD  - Laboratory of Neurobiology, Department of Surgery and Translational Medicine, 
      University of Milano-Bicocca, via Cadore 48, 20900 Monza, MB, Italy.
FAU - Saracchi, Enrico
AU  - Saracchi E
AD  - 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.
FAU - Fermi, Silvia
AU  - Fermi S
AD  - 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.
FAU - Brighina, Laura
AU  - Brighina L
AD  - Department of Neurology, San Gerardo Hospital, Monza, Italy.
FAU - Ferrarese, Carlo
AU  - Ferrarese C
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131219
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (HSC70 Heat-Shock Proteins)
RN  - 0 (HSPA8 protein, human)
RN  - 0 (LAMP2 protein, human)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (MEF2 Transcription Factors)
RN  - 0 (MEF2D protein, human)
SB  - IM
MH  - Aged
MH  - Autophagy/*physiology
MH  - Cell Survival
MH  - Female
MH  - HSC70 Heat-Shock Proteins/blood/*metabolism
MH  - Humans
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Lysosomal-Associated Membrane Protein 2/blood/metabolism
MH  - MEF2 Transcription Factors/blood/metabolism
MH  - Male
MH  - Middle Aged
MH  - Parkinson Disease/blood/*metabolism
OTO - NOTNLM
OT  - Chaperone-mediated autophagy
OT  - Hsc70
OT  - Lamp2a
OT  - MEF2D
OT  - Parkinson's disease
OT  - Peripheral blood mononuclear cell
EDAT- 2013/12/24 06:00
MHDA- 2014/09/10 06:00
CRDT- 2013/12/24 06:00
PHST- 2013/10/16 00:00 [received]
PHST- 2013/12/11 00:00 [revised]
PHST- 2013/12/12 00:00 [accepted]
PHST- 2013/12/24 06:00 [entrez]
PHST- 2013/12/24 06:00 [pubmed]
PHST- 2014/09/10 06:00 [medline]
AID - S0006-8993(13)01564-3 [pii]
AID - 10.1016/j.brainres.2013.12.017 [doi]
PST - ppublish
SO  - Brain Res. 2014 Feb 10;1546:46-52. doi: 10.1016/j.brainres.2013.12.017. Epub 2013 
      Dec 19.