Deep sequencing of sncRNAs reveals hallmarks and regulatory modules of the transcriptome during Parkinson's disease progression.
Nat Aging
; 1(3): 309-322, 2021 03.
Article
in En
| MEDLINE
| ID: mdl-37118411
ABSTRACT
Noncoding RNAs have diagnostic and prognostic importance in Parkinson's disease (PD). We studied circulating small noncoding RNAs (sncRNAs) in two large-scale longitudinal PD cohorts (Parkinson's Progression Markers Initiative (PPMI) and Luxembourg Parkinson's Study (NCER-PD)) and modeled their impact on the transcriptome. Sequencing of sncRNAs in 5,450 blood samples of 1,614 individuals in PPMI yielded 323 billion reads, most of which mapped to microRNAs but covered also other RNA classes such as piwi-interacting RNAs, ribosomal RNAs and small nucleolar RNAs. Dysregulated microRNAs associated with disease and disease progression occur in two distinct waves in the third and seventh decade of life. Originating predominantly from immune cells, they resemble a systemic inflammation response and mitochondrial dysfunction, two hallmarks of PD. Profiling 1,553 samples from 1,024 individuals in the NCER-PD cohort validated biomarkers and main findings by an independent technology. Finally, network analysis of sncRNA and transcriptome sequencing from PPMI identified regulatory modules emerging in patients with progressing PD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Parkinson Disease
/
MicroRNAs
/
RNA, Small Untranslated
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Aging
Year:
2021
Document type:
Article
Affiliation country:
Germany
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA