Autophagy dysfunction in peripheral blood mononuclear cells of Parkinson's disease 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 ³H-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.

Keywords: Chaperone-mediated autophagy; Lysosomes; Macroautophagy; Parkinson’s disease.