ABSTRACT
Parkinson's disease (PD) is a common neurodegenerative disorder which affects dopaminergic neurons leading to alteration of numerous cellular pathways. Several reports highlight that PD disturbs also other cells than CNS neurons including PBMCs, which could lead, among other things, to dysfunctions of immune functions. Because autophagy could be altered in PD, a monocentric pilot study was performed to quantify the transcripts levels of several autophagy genes in blood cells. MAP1LC3B, GABARAP, GABARAPL1, GABARAPL2 and P62/SQSTM1 were found to be overexpressed in patients. On the contrary, transcripts for HSPA8 and GAPDH were both decreased. Expression of MAP1LC3B and GABARAP was able to successfully segregate PD patients from healthy controls. The accuracy of this segregation was substantially increased when combined expressions of MAP1LC3B and GAPDH or GABARAP and GAPDH were used as categorical variables. This pilot study suggests that autophagy genes expression is dysregulated in PD patients and may open new perspectives for the characterisation of prediction markers.
Subject(s)
Autophagy/genetics , Parkinson Disease/genetics , Adaptor Proteins, Signal Transducing/genetics , Aged , Aged, 80 and over , Apoptosis Regulatory Proteins/genetics , Biomarkers/blood , Dopaminergic Neurons/metabolism , Female , France , Gene Expression/genetics , Gene Expression Profiling/methods , Gene Expression Regulation/genetics , Humans , Leukocytes, Mononuclear , Machine Learning , Male , Microtubule-Associated Proteins/genetics , Middle Aged , Parkinson Disease/blood , Pilot Projects , Sequestosome-1 Protein/geneticsABSTRACT
GALIG, an internal gene to the human galectin-3 gene, encodes two distinct proteins, Mitogaligin and Cytogaligin through translation of a unique mRNA in two overlapping alternative reading frames. When overexpressed GALIG induces apoptosis. In cultured cells, Mitogaligin destabilizes mitochondria membranes through interaction with cardiolipin. Little is known regarding the role of Cytogaligin. This protein displays multiple subcellular localizations; cytosol, nucleus, and mitochondria. We illustrate here that Cytogaligin is also secreted in the extracellular medium. Cytogaligin is shown to interact with α-Synuclein, the major component of Lewy bodies in Parkinson's disease. Overexpression of Cytogaligin reduces α-Synuclein dimerization raising a possible role in the evolution of α-Synuclein aggregation, a key molecular event underlying the pathogenesis of Parkinson's disease.
