Aim: The alpha-synuclein (α-syn) level in human cerebrospinal fluid (CSF), as measured by immunoassays, is promising as a Parkinson's disease (PD) biomarker. However, the levels of total α-syn are inconsistent among studies with large cohorts and different measurement platforms. Total α-syn level also does not correlate with disease severity or progression. Here, the authors developed a highly sensitive MRM method to measure absolute CSF α-syn peptide concentrations without prior enrichment or fractionation, aiming to discover new candidate biomarkers.
Results: Six peptides covering 73% of protein sequence were reliably identified, and two were consistently quantified in cross-sectional and longitudinal cohorts. Absolute concentration of α-syn in human CSF was determined to be 2.1 ng/mL. A unique α-syn peptide, TVEGAGSIAAATGFVK (81-96), displayed excellent correlation with previous immunoassay results in two independent PD cohorts (p < 0.001), correlated with disease severity, and its changes significantly tracked the disease progression longitudinally.
Conclusions: An MRM assay to quantify human CSF α-syn was developed and optimized. Sixty clinical samples from cross-sectional and longitudinal PD cohorts were analyzed with this approach. Although further larger scale validation is needed, the results suggest that α-syn peptide could serve as a promising biomarker in PD diagnosis and progression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540649 | PMC |
| http://dx.doi.org/10.1002/prca.201700045 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Profile and Usefulness of Serum Cytokines to Predict Prognosis in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.
Neurol Neuroimmunol Neuroinflamm
March 2025
Hospices Civils de Lyon, Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation-Hôpital Neurologique Pierre Wertheimer, Bron Cedex.
Objectives: To characterize the serum cytokine profile in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at onset and during follow-up and assess their utility for predicting relapses and disability.
Methods: This retrospective multicentric cohort study included patients aged 16 years and older meeting MOGAD 2023 criteria, with serum samples collected at baseline (≤3 months from disease onset) and follow-up (≥6 months from the baseline), and age-matched and time to sampling-matched patients with multiple sclerosis (MS). Eleven cytokines were assessed using the ELLA system.
Investigation of Natural Dyes and Taxonomic Identification of Fibers Used in Chancay Textiles by Vibrational Spectroscopy and Mass Spectrometry.
J Proteome Res
January 2025
Museum Conservation Institute, Smithsonian Institution, Suitland, Maryland 20746, United States.
Textiles provide a valuable source of information regarding past cultures and their artistic practices. Understanding ancient textiles requires identifying the raw materials used, since the origin of dyes and fibers may be from plants or animals, with the specific species used varying based on geography, trade routes and cultural significance. A selection of nine Chancay textile fragments attributed to 800-1200 CE were studied with liquid chromatography mass spectrometry (LC-MS) and direct analysis in real time mass spectrometry (DART-MS) to identify the chemical compounds in extracts of natural dyes used to create green, blue, red, yellow and black colors.
View Article and Find Full Text PDFIntelligent Hierarchical Targeting Near-Infrared Persistent Luminescence Nanosystem for Improved Nuclear Delivery and Simultaneous Visualization/Therapy of EBV-Associated Cancer.
ACS Appl Mater Interfaces
January 2025
Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China.
Epstein-Barr nuclear antigen 1 (EBNA1), a sequence-specific DNA binding protein of Epstein-Barr virus (EBV), is essential for viral genome replication and maintenance and is therefore an attractive target for the therapeutic intervention of EBV-associated cancers. Several EBNA1-specific inhibitors have demonstrated the ability to block EBNA1 function in vitro, but practical delivery strategies for these inhibitors in vivo are still lacking. Here, we report an intelligent hierarchical targeting theranostic nanosystem (denoted as mZGOCS@MnO-P5) that integrates an azide (N3) terminal dual-targeting peptide (N3-P5), a tumor microenvironment-responsive degradable MnO nanosheet, and a mesoporous ZnGaO:Cr, Sn near-infrared persistent luminescence (NIR-PL) nanosphere (mZGOCS).
View Article and Find Full Text PDFNEK7 phosphorylation amplifies NLRP3 inflammasome activation downstream of potassium efflux and gasdermin D.
Sci Immunol
January 2025
Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
The NLRP3 inflammasome plays a critical role in innate immunity and inflammatory diseases. NIMA-related kinase 7 (NEK7) is essential for inflammasome activation, and its interaction with NLRP3 is enhanced by K efflux. However, the mechanism by which K efflux promotes this interaction remains unknown.
View Article and Find Full Text PDFTRAMP assembly alters the conformation and RNA binding of Mtr4 and Trf4-Air2.
Proc Natl Acad Sci U S A
January 2025
Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX 75080.
The TRAMP complex contains two enzymatic activities essential for RNA processing upstream of the nuclear exosome. Within TRAMP, RNA is 3' polyadenylated by a subcomplex of Trf4/5 and Air1/2 and unwound 3' to 5' by Mtr4, a DExH helicase. The molecular mechanisms of TRAMP assembly and RNA shuffling between the two TRAMP catalytic sites are poorly understood.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!