Autophagy dysfunction in peripheral blood mononuclear cells of Parkinson's disease patients. (21st June 2019)

• Record Type: Journal Article
• Authors: Papagiannakis, Nikolaos; Xilouri, Maria; Koros, Christos; Simitsi, Athina-Maria; Stamelou, Maria; Maniati, Matina; Stefanis, Leonidas
• Is Part Of: Neuroscience letters. Volume 704(2019)
• Page Start: 112
• Page End: 115
• Publication Date: 2019-06-21
• Subjects: Parkinson's disease -- Lysosomes -- Chaperone-mediated autophagy -- Macroautophagy; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2019.04.003
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Protein degradation in cultured peripheral blood mononuclear cells is reduced in PD patients. Macroautophagy is impaired in PBMCs of PD patients. Chaperone-Mediated Autophagy is impaired in PBMCs of PD patients. Abstract: Background: Alpha-synuclein aggregation is considered one of the main causes of Parkinson's Disease (PD). Malfunction of autophagy-lysosomal pathways is believed to be an underlying mechanism of α-synuclein aggregation. Although such malfunction has been observed in PD brains, it is unclear whether it may also occur in extraneuronal tissues. Objectives: To assess lysosome-mediated protein degradation in cultured Peripheral Blood Mononuclear Cells (PBMCs) of PD patients and healthy controls. Methods: Total protein degradation in cultured PBMCs was measured by labelling the cells with 3 H-leucine using pulse-chase experiments. Different inhibitors were used to measure a range of autophagic pathways. Results: Protein degradation through the main autophagic pathways is reduced in PD patients (n = 18) compared to age- and sex-matched healthy controls (n = 18), (macroautophagy, p = .018; Chaperone-Mediated autophagy, p = .04; and total lysosomal function, p = .007). Conclusions: Lysosomal dysfunction is present in cultured PBMCs of PD patients, suggesting that it may reflect a systemic feature of the disease.