期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ijms22052737
关键词
Alzheimer’ s disease; Parkinson’ s disease; amyotrophic lateral sclerosis; frontotemporal dementia; large extracellular vesicles; small extracellular vesicles; RNA-seq; miRNAs
资金
- Italian Ministry of Health [GR-2016-02361552]
- Fondazione Regionale per la Ricerca Biomedica for TRANS-ALS [FRRB 2015-0023]
- Fondazione Cariplo 2017 (Extracellular vesicles in the pathogenesis of Frontotemporal Dementia) [2017-0747]
- Association between frailty trajectories and biological markers of aging [2017-0557]
Identifying biomarkers for neurodegenerative diseases through analyzing the miRNA signatures in plasma-derived LEVs and SEVs from AD, PD, ALS, and FTD patients can differentiate various NDs and provide insights into different pathways involved in each disease.
Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miRNA signatures in plasma derived LEVs and SEVs of Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD) patients. LEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and differential centrifugation and RNA was extracted. Small RNAs libraries were carried out by Next Generation Sequencing (NGS). MiRNAs discriminate all NDs diseases from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were instead linked to ubiquitin mediated proteolysis and Toll-like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway. LEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading of the disease. The study of common and different miRNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration.
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