Long Noncoding RNA POU3F3 and α-Synuclein in Plasma L1CAM Exosomes Combined with β-Glucocerebrosidase Activity: Potential Predictors of Parkinson's Disease

Long noncoding RNAs (lncRNAs) are implicated in the autophagic-lysosomal pathway (ALP) and are closely linked to Parkinson's disease (PD) pathology. β-Glucocerebrosidase (GCase) has also been reported to be correlated with α-synuclein (α-syn) proteostasis. However, lncRNAs and α-syn in neural-d...

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Published in:Neurotherapeutics Vol. 17; no. 3; pp. 1104 - 1119
Main Authors: Zou, Jing, Guo, Yue, Wei, Lei, Yu, Fang, Yu, Bo, Xu, Anding
Format: Journal Article
Language:English
Published: Cham Elsevier Inc 01.07.2020
Springer International Publishing
Springer Nature B.V
Subjects:
Aged
alpha-Synuclein - blood
Autophagic-lysosomal pathway
Biomarkers - blood
Biomarkers - metabolism
Biomedical and Life Sciences
Biomedicine
Cognitive ability
Cross-Sectional Studies
Enzyme Activation - physiology
Exosomes
Exosomes - metabolism
Female
Glucosylceramidase
Glucosylceramidase - blood
Glucosylceramidase - metabolism
Humans
L1CAM exosomes
Linc-POU3F3
Male
Middle Aged
Movement disorders
Nanoparticles
Neural Cell Adhesion Molecule L1 - blood
Neurobiology
Neurodegenerative diseases
Neurology
Neurosciences
Neurosurgery
Original
Original Article
Parkinson Disease - blood
Parkinson Disease - diagnosis
Parkinson's disease
POU Domain Factors - blood
Predictive Value of Tests
Ribonucleic acid
RNA
Synuclein
α-synuclein
Linc-POU3F3
Autophagic-lysosomal pathway
Parkinson's disease
L1CAM exosomes
α-synuclein
Parkinson’s disease
ISSN:1878-7479, 1933-7213, 1878-7479
Online Access:Get full text
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Abstract Long noncoding RNAs (lncRNAs) are implicated in the autophagic-lysosomal pathway (ALP) and are closely linked to Parkinson's disease (PD) pathology. β-Glucocerebrosidase (GCase) has also been reported to be correlated with α-synuclein (α-syn) proteostasis. However, lncRNAs and α-syn in neural-derived L1CAM exosomes and GCase activity in the plasma of PD patients have not been studied. This study used an ultrasensitive methodology, fluorescence nanoparticle tracking analysis (NTA), to measure plasma L1CAM exosomes and Quanterix Simoa to measure α-syn concentrations in L1CAM exosomes. Eighty-five healthy controls and 93 PD patients were enrolled, and several scales were used to rate the severity of PD. Receiver operating characteristic (ROC) curves were applied to map the diagnostic accuracy of categorizing PD patients and healthy subjects. We found increased Linc-POU3F3 and α-syn concentrations in L1CAM exosomes and decreased GCase activity in PD patients compared with controls. The three biomarkers displayed obvious differences among PD patients based on gender, H-Y stage, and UPDRS-III distribution. Interestingly, Linc-POU3F3 was significantly positively correlated with α-syn in L1CAM exosomes and inversely correlated with GCase activity in PD patients. Significant correlations were observed among L1CAM exosomal Linc-POU3F3 levels, GCase activity, and PD severity, including motor/cognitive dysfunction. Additionally, the combination of Linc-POU3F3 and α-syn in L1CAM exosomes and GCase activity could discriminate PD patients from controls. These results suggest that L1CAM exosomal Linc-POU3F3, L1CAM exosomal α-syn, and GCase activity may shed light on the mechanism underlying the autophagic-lysosomal system in the pathogenesis of PD and could be used to assess the severity of PD.
AbstractList Long noncoding RNAs (lncRNAs) are implicated in the autophagic-lysosomal pathway (ALP) and are closely linked to Parkinson’s disease (PD) pathology. β-Glucocerebrosidase (GCase) has also been reported to be correlated with α-synuclein (α-syn) proteostasis. However, lncRNAs and α-syn in neural-derived L1CAM exosomes and GCase activity in the plasma of PD patients have not been studied. This study used an ultrasensitive methodology, fluorescence nanoparticle tracking analysis (NTA), to measure plasma L1CAM exosomes and Quanterix Simoa to measure α-syn concentrations in L1CAM exosomes. Eighty-five healthy controls and 93 PD patients were enrolled, and several scales were used to rate the severity of PD. Receiver operating characteristic (ROC) curves were applied to map the diagnostic accuracy of categorizing PD patients and healthy subjects. We found increased Linc-POU3F3 and α-syn concentrations in L1CAM exosomes and decreased GCase activity in PD patients compared with controls. The three biomarkers displayed obvious differences among PD patients based on gender, H-Y stage, and UPDRS-III distribution. Interestingly, Linc-POU3F3 was significantly positively correlated with α-syn in L1CAM exosomes and inversely correlated with GCase activity in PD patients. Significant correlations were observed among L1CAM exosomal Linc-POU3F3 levels, GCase activity, and PD severity, including motor/cognitive dysfunction. Additionally, the combination of Linc-POU3F3 and α-syn in L1CAM exosomes and GCase activity could discriminate PD patients from controls. These results suggest that L1CAM exosomal Linc-POU3F3, L1CAM exosomal α-syn, and GCase activity may shed light on the mechanism underlying the autophagic-lysosomal system in the pathogenesis of PD and could be used to assess the severity of PD.
Long noncoding RNAs (lncRNAs) are implicated in the autophagic-lysosomal pathway (ALP) and are closely linked to Parkinson's disease (PD) pathology. β-Glucocerebrosidase (GCase) has also been reported to be correlated with α-synuclein (α-syn) proteostasis. However, lncRNAs and α-syn in neural-derived L1CAM exosomes and GCase activity in the plasma of PD patients have not been studied. This study used an ultrasensitive methodology, fluorescence nanoparticle tracking analysis (NTA), to measure plasma L1CAM exosomes and Quanterix Simoa to measure α-syn concentrations in L1CAM exosomes. Eighty-five healthy controls and 93 PD patients were enrolled, and several scales were used to rate the severity of PD. Receiver operating characteristic (ROC) curves were applied to map the diagnostic accuracy of categorizing PD patients and healthy subjects. We found increased Linc-POU3F3 and α-syn concentrations in L1CAM exosomes and decreased GCase activity in PD patients compared with controls. The three biomarkers displayed obvious differences among PD patients based on gender, H-Y stage, and UPDRS-III distribution. Interestingly, Linc-POU3F3 was significantly positively correlated with α-syn in L1CAM exosomes and inversely correlated with GCase activity in PD patients. Significant correlations were observed among L1CAM exosomal Linc-POU3F3 levels, GCase activity, and PD severity, including motor/cognitive dysfunction. Additionally, the combination of Linc-POU3F3 and α-syn in L1CAM exosomes and GCase activity could discriminate PD patients from controls. These results suggest that L1CAM exosomal Linc-POU3F3, L1CAM exosomal α-syn, and GCase activity may shed light on the mechanism underlying the autophagic-lysosomal system in the pathogenesis of PD and could be used to assess the severity of PD.Long noncoding RNAs (lncRNAs) are implicated in the autophagic-lysosomal pathway (ALP) and are closely linked to Parkinson's disease (PD) pathology. β-Glucocerebrosidase (GCase) has also been reported to be correlated with α-synuclein (α-syn) proteostasis. However, lncRNAs and α-syn in neural-derived L1CAM exosomes and GCase activity in the plasma of PD patients have not been studied. This study used an ultrasensitive methodology, fluorescence nanoparticle tracking analysis (NTA), to measure plasma L1CAM exosomes and Quanterix Simoa to measure α-syn concentrations in L1CAM exosomes. Eighty-five healthy controls and 93 PD patients were enrolled, and several scales were used to rate the severity of PD. Receiver operating characteristic (ROC) curves were applied to map the diagnostic accuracy of categorizing PD patients and healthy subjects. We found increased Linc-POU3F3 and α-syn concentrations in L1CAM exosomes and decreased GCase activity in PD patients compared with controls. The three biomarkers displayed obvious differences among PD patients based on gender, H-Y stage, and UPDRS-III distribution. Interestingly, Linc-POU3F3 was significantly positively correlated with α-syn in L1CAM exosomes and inversely correlated with GCase activity in PD patients. Significant correlations were observed among L1CAM exosomal Linc-POU3F3 levels, GCase activity, and PD severity, including motor/cognitive dysfunction. Additionally, the combination of Linc-POU3F3 and α-syn in L1CAM exosomes and GCase activity could discriminate PD patients from controls. These results suggest that L1CAM exosomal Linc-POU3F3, L1CAM exosomal α-syn, and GCase activity may shed light on the mechanism underlying the autophagic-lysosomal system in the pathogenesis of PD and could be used to assess the severity of PD.
Author Zou, Jing
Yu, Bo
Xu, Anding
Wei, Lei
Guo, Yue
Yu, Fang
Author_xml – sequence: 1
  givenname: Jing
  surname: Zou
  fullname: Zou, Jing
  organization: Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 510630, Guangzhou, Guangdong, People's Republic of China
– sequence: 2
  givenname: Yue
  surname: Guo
  fullname: Guo, Yue
  organization: Key Laboratory of Assisted Circulation, The First Affiliated Hospital of Sun Yat-Sen University, 510080, Guangzhou, Guangdong, People's Republic of China
– sequence: 3
  givenname: Lei
  surname: Wei
  fullname: Wei, Lei
  organization: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, 510630, Guangzhou, Guangdong, People's Republic of China
– sequence: 4
  givenname: Fang
  surname: Yu
  fullname: Yu, Fang
  organization: Department of Neurology, University of Pittsburgh, 15213, Pittsburgh, Pennsylvania, USA
– sequence: 5
  givenname: Bo
  surname: Yu
  fullname: Yu, Bo
  organization: Department of Medicine, Lincoln Medical Center, 10451, Bronx, New York, USA
– sequence: 6
  givenname: Anding
  orcidid: 0000-0003-3154-0985
  surname: Xu
  fullname: Xu, Anding
  email: tlil@jnu.edu.cn
  organization: Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 510630, Guangzhou, Guangdong, People's Republic of China
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32236821$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright 2020 The American Society for Experimental NeuroTherapeutics, Inc.
The American Society for Experimental NeuroTherapeutics, Inc. 2020
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Issue 3
Keywords Linc-POU3F3
Autophagic-lysosomal pathway
Parkinson's disease
L1CAM exosomes
α-synuclein
Parkinson’s disease
Language English
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PublicationSubtitle The Journal of the American Society for Experimental Neurotherapeutics
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Snippet Long noncoding RNAs (lncRNAs) are implicated in the autophagic-lysosomal pathway (ALP) and are closely linked to Parkinson's disease (PD) pathology....
Long noncoding RNAs (lncRNAs) are implicated in the autophagic-lysosomal pathway (ALP) and are closely linked to Parkinson’s disease (PD) pathology....
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SubjectTerms Aged
alpha-Synuclein - blood
Autophagic-lysosomal pathway
Biomarkers - blood
Biomarkers - metabolism
Biomedical and Life Sciences
Biomedicine
Cognitive ability
Cross-Sectional Studies
Enzyme Activation - physiology
Exosomes
Exosomes - metabolism
Female
Glucosylceramidase
Glucosylceramidase - blood
Glucosylceramidase - metabolism
Humans
L1CAM exosomes
Linc-POU3F3
Male
Middle Aged
Movement disorders
Nanoparticles
Neural Cell Adhesion Molecule L1 - blood
Neurobiology
Neurodegenerative diseases
Neurology
Neurosciences
Neurosurgery
Original
Original Article
Parkinson Disease - blood
Parkinson Disease - diagnosis
Parkinson's disease
POU Domain Factors - blood
Predictive Value of Tests
Ribonucleic acid
RNA
Synuclein
α-synuclein
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Title Long Noncoding RNA POU3F3 and α-Synuclein in Plasma L1CAM Exosomes Combined with β-Glucocerebrosidase Activity: Potential Predictors of Parkinson's Disease
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