Identification of distinct circulating exosomes in Parkinson's disease

Abstract

ObjectiveWhether circulating microvesicles convey bioactive signals in neurodegenerative diseases remains currently unknown. In this study, we investigated the biochemical composition and biological function of exosomes isolated from sera of patients with Parkinson's disease (PD).MethodsProteomic analysis was performed on microvesicle preparations from grouped samples of patients with genetic and sporadic forms of PD, amyotrophic lateral sclerosis, and healthy subjects. Nanoparticle-tracking analysis was used to assess the number and size of exosomes between patient groups. To interrogate their biological effect, microvesicles were added to primary rat cortical neurons subjected to either nutrient deprivation or sodium arsenite.ResultsAmong 1033 proteins identified, 23 exosome-associated proteins were differentially abundant in PD, including the regulator of exosome biogenesis syntenin 1. These protein changes were detected despite similar exosome numbers across groups suggesting that they may reflect exosome subpopulations with distinct functions. Accordingly, we showed in models of neuronal stress that Parkinson's-derived microvesicles have a protective effect.InterpretationCollectively, these data suggest for the first time that immunophenotyping of circulating exosome subpopulations in PD may lead to a better understanding of the systemic response to neurodegeneration and the development of novel therapeutics.

Impact of lysosome status on extracellular vesicle content and release

“…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). The discovery of differences in disease-related proteins in EVs isolated from biological fluids of patients and control subjects might lead to early diagnosis and disease prognosis of neurodegenerative disorders.…”

Mitochondrial Reprogramming Regulates Breast Cancer Progression

“…Syntenin is among the top 20 proteins most abundantly expressed in the exosomes and epithelial cell cancers (48)(49)(50). Thus, syntenin could serve as a reliable exosome marker.…”

MDA‐9/Syntenin Control

“…). In a recent study, MDA‐9/Syntenin was also identified as one of the top 23 proteins differentially expressed in the circulating exosomes of patients with Parkinson's disease (Tomlinson et al, ). Of note, MDA‐9/Syntenin was detected in the exosomes derived from the human melanoma cells and cerebrospinal fluids (Xiao et al, ; Chiasserini et al, ).…”