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Lysosomal alterations in peripheral blood mononuclear cells of Parkinson's disease patients
Author(s) -
Papagiannakis Nikolaos,
Xilouri Maria,
Koros Christos,
Stamelou Maria,
Antonelou Roubina,
Maniati Matina,
Papadimitriou Dimitra,
Moraitou Marina,
Michelakakis Helen,
Stefanis Leonidas
Publication year - 2015
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.26433
Subject(s) - glucocerebrosidase , peripheral blood mononuclear cell , autophagy , lysosome , endocrinology , alpha synuclein , biology , parkinson's disease , mutation , chaperone (clinical) , medicine , gene , disease , biochemistry , enzyme , pathology , in vitro , apoptosis
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. © 2015 International Parkinson and Movement Disorder Society