Shotgun Proteomics Links Proteoglycan-4 ⁺ Extracellular Vesicles to Cognitive Protection in Amyotrophic Lateral Sclerosis.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

Amyotrophic Lateral Sclerosis*/metabolism ; Amyotrophic Lateral Sclerosis*/blood ; Extracellular Vesicles*/metabolism ; Proteomics*/methods ; Biomarkers*/blood ; Biomarkers*/metabolism; Humans ; Male ; Middle Aged ; Female ; Aged ; Proteoglycans/metabolism ; Cognition ; Case-Control Studies ; Adult

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder lacking reliable biomarkers for early diagnosis and disease progression monitoring. This study aimed to identify the novel biomarkers in plasmatic extracellular vesicles (EVs) isolated from ALS patients and healthy controls (HCs). A total of 61 ALS patients and 30 age-matched HCs were enrolled in the study and the protein content of circulating EVs was analyzed by shotgun proteomics. The study was divided into a discovery phase (involving 12 ALS and 12 HC patients) and a validation one (involving 49 ALS and 20 HC patients). In the discovery phase, more than 300 proteins were identified, with 32 proteins showing differential regulation in ALS patients compared to HCs. In the validation phase, over 400 proteins were identified, with 20 demonstrating differential regulation in ALS patients compared to HCs. Notably, seven proteins were found to be common to both phases, all of which were significantly upregulated in EVs from ALS patients. Most of them have previously been linked to ALS since they have been detected in the serum or cerebrospinal fluid of ALS patients. Among them, proteoglycan (PRG)-4, also known as lubricin, was of particular interest since it was significantly increased in ALS patients with normal cognitive and motor functions. This study highlights the significance of EVs as a promising avenue for biomarker discovery in ALS. Moreover, it sheds light on the unexpected role of PRG-4 in relation to cognitive status in ALS patients.

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953121 European Union's Horizon 2020 Research and Innovation Program; FOHN Ministero dell'Istruzione e del Merito; AGING Ministero dell'Istruzione e del Merito

Keywords: amyotrophic lateral sclerosis (ALS); cognition; cognitive impairment; extracellular vesicles (EVs); proteoglycan 4 (PRG-4); proteomics

0 (Biomarkers)
0 (Proteoglycans)

Date Created: 20240627 Date Completed: 20240627 Latest Revision: 20240717

20240717

PMC11202157

10.3390/biom14060727

38927130