ArticleBrain communications2021
Analysis of circulating protein aggregates as a route of investigation into neurodegenerative disorders.
Article in Brain communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Multi-omics-based decoding of circulating biomarkers in amyotrophic lateral sclerosis and risks in environmental toxins.BMC pharmacology & toxicology · 2025Article
- Neuroprotective Potential ofNutrients · 2025Article
- Targeting Protein Aggregation in ALS.Biomolecules · 2024Review
- Mass Spectrometry-Based Characterization of Protein Aggregates in Tissues and Biofluids.Advances in experimental medicine and biology · 2024Article
- CSF neurofilament light chain profiling and quantitation in neurological diseases.Brain communications · 2024Article
- Label-free fibre optic Raman spectroscopy with bounded simplex-structured matrix factorization for the serial study of serum in amyotrophic lateral sclerosis.The Analyst · 2022Article
- Blood biomarkers in ALS: challenges, applications and novel frontiers.Acta neurologica Scandinavica · 2022Review
- Cerebral malaria - modelling interactions at the blood-brain barrier in vitro.Disease models & mechanisms · 2022Review
- Bacteria-Derived Protein Aggregates Contribute to the Disruption of Host Proteostasis.International journal of molecular sciences · 2022Article
- Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Plasma proteome composition reflects the inflammatory and metabolic state of the organism and can be predictive of system-level and organ-specific pathologies. Circulating protein aggregates are enriched with neurofilament heavy chain-axonal proteins involved in brain aggregate formation and recently identified as biomarkers of the fatal neuromuscular disorder amyotrophic lateral sclerosis. Using unbiased proteomic methods, we have fully characterized the content in neuronal proteins of circulating protein aggregates from amyotrophic lateral sclerosis patients and healthy controls, with reference to brain protein aggregate composition. We also investigated circulating protein aggregate protein aggregation propensity, stability to proteolytic digestion and toxicity for neuronal and endothelial cell lines. Circulating protein aggregates separated by ultracentrifugation are visible as electron-dense macromolecular particles appearing as either large globular or as small filamentous formations. Analysis by mass spectrometry revealed that circulating protein aggregates obtained from patients are enriched with proteins involved in the proteasome system, possibly reflecting the underlying basis of dysregulated proteostasis seen in the disease, while those from healthy controls show enrichment of proteins involved in metabolism. Compared to the whole human proteome, proteins within circulating protein aggregates and brain aggregates show distinct chemical features of aggregation propensity, which appear dependent on the tissue or fluid of origin and not on the health status. Neurofilaments' two high-mass isoforms (460 and 268 kDa) showed a strong differential expression in amyotrophic lateral sclerosis compared to healthy control circulating protein aggregates, while aggregated neurofilament heavy chain was also partially resistant to enterokinase proteolysis in patients, demonstrated by immunoreactive bands at 171 and 31 kDa fragments not seen in digested healthy controls samples. Unbiased proteomics revealed that a total of 4973 proteins were commonly detected in circulating protein aggregates and brain, including 24 expressed from genes associated with amyotrophic lateral sclerosis. Interestingly, 285 circulating protein aggregate proteins (5.7%) were regulated (
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