ArticleInflammation and regeneration2024
Proteomic insights into extracellular vesicles in ALS for therapeutic potential of Ropinirole and biomarker discovery.
Article in Inflammation and regeneration, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Extracellular vesicles as a liquid biopsy for amyotrophic lateral sclerosis: a systematic review and meta-analysis.Journal of translational medicine · 2026Pooled it
- Human iPSC‑based translational and reverse translational research for neurodegenerative diseases: emphasis on ALS and key advances.Japanese journal of radiology · 2026Review
- The New Spine of Access to the Brain's Secrets: Extracellular Vesicles from Cerebrospinal Fluid Liquid Biopsies in CNS Diseases and Blood-Brain Barrier Research.Molecular neurobiology · 2026Review
- Diagnostic potential of cryptic exon-derived peptides in serum extracellular vesicles for sporadic amyotrophic lateral sclerosis.Inflammation and regeneration · 2026Article
- Review
- Tetraspanin-based immunocapture for high-depth proteomic profiling of extracellular vesicles from cerebrospinal fluid for biomarker discovery.Clinical proteomics · 2026Article
- Machine learning for extracellular vesicles enables diagnostic and therapeutic nanobiotechnology.Journal of nanobiotechnology · 2026Review
- Unveiling the Proteomic Landscape of Extracellular Vesicles: Implications for Neurodegeneration and Neuroprotection.Journal of neurochemistry · 2026Review
- Sephin1 reduces TDP-43 cytoplasmic mislocalization and improves motor neuron survival in ALS models.Life science alliance · 2025Article
- Evaluation of serum samples in long cryopreservation for SomaScan proteomics and sex differences in elderly Japanese adults.Scientific reports · 2025Observational
- Ropinirole Functions Through a Dopamine Receptor D2-Independent Mechanism to Ameliorate Amyotrophic Lateral Sclerosis Phenotypes in TARDBP-Mutant iPSC-Derived Motor Neurons.Journal of neurochemistry · 2025Article
- Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential.Molecular neurodegeneration · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
backgroundExtracellular vesicles (EVs) hold the potential for elucidating the pathogenesis of amyotrophic lateral sclerosis (ALS) and serve as biomarkers. Notably, the comparative and longitudinal alterations in the protein profiles of EVs in serum (sEVs) and cerebrospinal fluid (CSF; cEVs) of sporadic ALS (SALS) patients remain uncharted. Ropinirole hydrochloride (ROPI; dopamine D2 receptor [D2R] agonist), a new anti-ALS drug candidate identified through induced pluripotent stem cell (iPSC)-based drug discovery, has been suggested to inhibit ALS disease progression in the Ropinirole Hydrochloride Remedy for Amyotrophic Lateral Sclerosis (ROPALS) trial, but its mechanism of action is not well understood. Therefore, we tried to reveal longitudinal changes with disease progression and the effects of ROPI on protein profiles of EVs.
methodsWe collected serum and CSF at fixed intervals from ten controls and from 20 SALS patients participating in the ROPALS trial. Comprehensive proteomic analysis of EVs, extracted from these samples, was conducted using liquid chromatography/mass spectrometer (LC/MS). Furthermore, we generated iPSC-derived astrocytes (iPasts) and performed RNA sequencing on astrocytes with or without ROPI treatment.
resultsThe findings revealed notable disparities yet high congruity in sEVs and cEVs protein profiles concerning disease status, time and ROPI administration. In SALS, both sEVs and cEVs presented elevated levels of inflammation-related proteins but reduced levels associated with unfolded protein response (UPR). These results mirrored the longitudinal changes after disease onset and correlated with the revised ALS Functional Rating Scale (ALSFRS-R) at sampling time, suggesting a link to the onset and progression of SALS. ROPI appeared to counteract these changes, attenuating inflammation-related protein levels and boosting those tied to UPR in SALS, proposing an anti-ALS impact on EV protein profiles. Reverse translational research using iPasts indicated that these changes may partly reflect the DRD2-dependent neuroinflammatory inhibitory effects of ROPI. We have also identified biomarkers that predict diagnosis and disease progression by machine learning-driven biomarker search.
conclusionsDespite the limited sample size, this study pioneers in reporting time-series proteomic alterations in serum and CSF EVs from SALS patients, offering comprehensive insights into SALS pathogenesis, ROPI-induced changes, and potential prognostic and diagnostic biomarkers.
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