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

Ho, Dong Hwan; Yi, SangHak; Seo, Hyemyung; Son, Ilhong; Seol, Wongi

doi:10.1155/2014/704678

Cited by 78 publications

(74 citation statements)

References 38 publications

(65 reference statements)

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“…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).…”

Section: R E V I E W S E R I E S : E X T R a C E L L U L A R V E S I mentioning

confidence: 99%

Extracellular vesicles and intercellular communication within the nervous system

Zappulli¹,

Friis²,

Fitzpatrick³

et al. 2016

Journal of Clinical Investigation

199

162

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Section: R E V I E W S E R I E S : E X T R a C E L L U L A R V E S I mentioning

confidence: 99%

Extracellular vesicles and intercellular communication within the nervous system

Zappulli¹,

Friis²,

Fitzpatrick³

et al. 2016

Journal of Clinical Investigation

199

162

View full text Add to dashboard Cite

“…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).…”

Section: Neurodegenerative Disordersmentioning

confidence: 99%

Impact of lysosome status on extracellular vesicle content and release

Eitan

Suire

Shi

et al. 2016

Ageing Research Reviews

209

161

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Extracellular vesicles (EVs) are nanoscale size bubble-like membranous structures released from cells. EVs contain RNA, lipids and proteins and are thought to serve various roles including intercellular communication and removal of misfolded proteins. The secretion of misfolded and aggregated proteins in EVs may be a cargo disposal alternative to the autophagy-lysosomal and ubiquitin-proteasome pathways. In this review we will discuss the importance of lysosome functionality for the regulation of EV secretion and content. Exosomes are a subtype of EVs that are released by the fusion of multivesicular bodies (MVB) with the plasma membrane. MVBs can also fuse with lysosomes, and the trafficking pathway of MVBs can therefore determine whether or not exosomes are released from cells. Here we summarize data from studies of the effects of lysosome inhibition on the secretion of EVs and on the possibility that cells compensate for lysosome malfunction by disposal of potentially toxic cargos in EVs. A better understanding of the molecular mechanisms that regulate trafficking of MVBs to lysosomes and the plasma membrane may advance an understanding of diseases in which pathogenic proteins, lipids or infectious agents accumulate within or outside of cells.

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“…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.…”

mentioning

confidence: 99%

Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019S LRRK2 carriers

et al. 2016

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Objective: To test whether phosphorylated Ser-1292 LRRK2 levels in urine exosomes predicts LRRK2 mutation carriers (LRRK21) and noncarriers (LRRK22) with Parkinson disease (PD1) and without Parkinson disease (PD2).Methods: LRRK2 protein was purified from urinary exosomes collected from participants in 2 independent cohorts. The first cohort included 14 men (LRRK21/PD1, n 5 7; LRRK22/PD1, n 5 4; LRRK22/PD2, n 5 3). The second cohort included 62 men (LRRK22/PD2, n 5 16; LRRK21/PD2, n 5 16; LRRK21/PD1, n 5 14; LRRK22/PD1, n 5 16). The ratio of Ser(P)-1292 LRRK2 to total LRRK2 was compared between LRRK21/PD1 and LRRK22 in the first cohort and between LRRK2 G2019S carriers with and without PD in the second cohort.Results: LRRK21/PD1 had higher ratios of Ser(P)-1292 LRRK2 to total LRRK2 than LRRK22/PD2 (4.8-fold, p , 0.001) and LRRK22/PD1 (4.6-fold, p , 0.001). Among mutation carriers, those with PD had higher Ser(P)-1292 LRRK2 to total LRRK2 than those without PD (2.2-fold, p , 0.001). Ser(P)-1292 LRRK2 levels predicted symptomatic from asymptomatic carriers with an area under the receiver operating characteristic curve of 0.844. Conclusion:Elevated ratio of phosphorylated Ser-1292 LRRK2 to total LRRK2 in urine exosomes predicted LRRK2 mutation status and PD risk among LRRK2 mutation carriers. Future studies may explore whether interventions that reduce this ratio may also reduce PD risk.

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

Cited by 78 publications

References 38 publications

Extracellular vesicles and intercellular communication within the nervous system

Extracellular vesicles and intercellular communication within the nervous system

Impact of lysosome status on extracellular vesicle content and release

Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019S LRRK2 carriers

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