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| Home > Articles > Published articles > Neuroinflammation-Related Proteins NOD2 and Spp1 Are Abnormally Upregulated in Amyotrophic Lateral Sclerosis |
| Home > Articles > Published articles > Neuroinflammation-Related Proteins NOD2 and Spp1 Are Abnormally Upregulated in Amyotrophic Lateral Sclerosis |
(Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau)| Date: | 2022 |
| Abstract: | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown etiology and poorly understood pathophysiology. There is no specific biomarker either for diagnosis or prognosis. The aim of our study was to investigate differentially expressed proteins in the CSF and serum from patients with ALS to determine their role in the disease process and evaluate their utility as diagnostic or prognostic biomarkers. We performed mass spectrometry in the CSF from 3 patients with ALS and 3 healthy controls (HCs). The results were compared with motor cortex dysregulated transcripts obtained from 11patients with sporadic ALS and 8 HCs. Candidate proteins were tested using ELISA in the serum of 123 patients with ALS, 30 patients with Alzheimer disease (AD), 28 patients with frontotemporal dementia (FTD), and 102 HCs. Patients with ALS, AD, and FTD were prospectively recruited from January 2003 to December 2020. A group of age-matched HCs was randomly selected from the Sant Pau Initiative on Neurodegeneration cohort of the Sant Pau Memory Unit. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and osteopontin (Spp1) were differentially expressed in the CSF and the motor cortex transcriptome of patients with ALS compared with that in HCs (p < 0. 05). NOD2 and Spp1 levels were significantly higher in sera from patients with ALS than in HCs (p < 0. 001). Receiver operating characteristic analysis showed an area under the curve of 0. 63 for NOD2 and 0. 81 for Spp1. NOD2 levels were significantly lower in patients with AD and FTD than in patients with ALS (p < 0. 0001), but we found no significant differences in Spp1 levels between patients with ALS, AD (p = 0. 51), and FTD (p = 0. 42). We found a negative correlation between Spp1 levels and ALS functional rating scale (r = −0. 24, p = 0. 009). Our discovery-based approach identified NOD2 as a novel biomarker in ALS and adds evidence to the contribution of Spp1 in the disease process. Both proteins are involved in innate immunity and autophagy and are increased in the serum from patients with ALS. Our data support a relevant role of neuroinflammation in the pathophysiology of the disease and may identify targets for disease-modifying treatments in ALS. Further longitudinal studies should investigate the diagnostic and prognostic value of NOD2 and Spp1 in clinical practice. |
| Grants: | Instituto de Salud Carlos III PI 15/01618 Instituto de Salud Carlos III PI 19/01543 Instituto de Salud Carlos III cm 21/00057 Instituto de Salud Carlos III JR 19/00037 Instituto de Salud Carlos III JR 20/0018 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Published in: | Neurology® neuroimmunology & neuroinflammation, Vol. 10 (december 2022) , ISSN 2332-7812 |
