Increased DJ-1 in Urine Exosome of Korean Males with Parkinson’s Disease

Abstract

Parkinson's disease (PD) is a difficult disease to diagnose although it is the second most common neurodegenerative disease. Recent studies show that exosome isolated from urine contains LRRK2 or DJ-1, proteins whose mutations cause PD. To investigate a potential use for urine exosomes as a tool for PD diagnosis, we compared levels of LRRK2, α-synuclein, and DJ-1 in urine exosomes isolated from Korean PD patients and non-PD controls. LRRK2 and DJ-1, but not α-synuclein, were detected in the urine exosome samples, as reported previously. We initially could not detect any significant difference in these protein levels between the patient and the control groups. However, when age, disease duration, L-dopa daily dose, and gender were considered as analytical parameters, LRRK2 and DJ-1 protein levels showed clear gender-dependent differences. In addition, DJ-1 level was significantly higher (1.7-fold) in male patients with PD than that in male non-PD controls and increased in an age-dependent manner in male patients with PD. Our observation might provide a clue to lead to a novel biomarker for PD diagnosis, at least in males.

Extracellular vesicles and intercellular communication within the nervous system

“…CSF EVs from patients with ALS have elevated TDP-43 (81). Increased levels of the PD-associated proteins deglycase DJ-1 and leucine-rich repeat kinase 2 (LRRK2) have been found in bloodderived EVs in patients with PD (82,83). Brain-derived EVs in the blood represent a small fraction of the total EV content, most of which is derived from vascular-associated cells (84).…”

Impact of lysosome status on extracellular vesicle content and release

“…In addition, a significant correlation is found between the level of plasma EV-associated α-synuclein and disease severity (Shi, Liu et al 2014). Two additional proteins that are linked to PD, DJ-1 and LRRK2 are also detected in EVs isolated from urine samples from PD patients, and the level of DJ-1 is significantly higher in patients compared to control subjects (Ho, Yi et al 2014). Furthermore, levels of syntenin 1, which is a regulator of EV biogenesis, are greater in EVs isolated from blood of PD patients (Tomlinson, Zheng et al 2015).…”

Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019S LRRK2 carriers

“…Previously, we and others identified urine exosomes as a stable source of LRRK2 protein in clinical populations. 12,13 In the present study, we utilized urine exosomes to determine whether Ser(P)-1292 LRRK2 levels predict LRRK2 G2019S mutation status and PD diagnosis.…”