Inflammasome in ALS skeletal muscle: NLRP3 as a potential biomarker

Moreno-García, L. (Universidad de Zaragoza) ; Miana-Mena, F.J. (Universidad de Zaragoza) ; Moreno-Martínez, L. (Universidad de Zaragoza) ; de la Torre, M. (Universidad de Zaragoza) ; Lunetta, C. ; Tarlarini, C. ; Zaragoza, P. (Universidad de Zaragoza) ; Calvo, A.C. (Universidad de Zaragoza) ; Osta, R. (Universidad de Zaragoza)

Resumen: Since NLRP3 inflammasome plays a pivotal role in several neurodegenerative disorders, we hypothesized that levels of inflammasome components could help in diagnosis or prognosis of amyotrophic lateral sclerosis (ALS). Gene and protein expression was assayed by RT-PCR and Western blot. Spearman’s correlation coefficient was used to determine the linear correlation of transcriptional expression levels with longevity throughout disease progression in mice models. Kaplan-Meier analysis was performed to evaluate MCC950 effects (NLRP3 inhibitor) on lifespan of SOD1G93A mice. The results showed significant alterations in NLRP3 inflammasome gene and protein levels in the skeletal muscle of SOD1G93A mice. Spearman’s correlation coefficient revealed a positive association between Nlrp3 transcriptional levels in skeletal muscle and longevity of SOD1G93A mice (r = 0.506; p = 0.027). Accordingly, NLRP3 inactivation with MCC950 decreased the lifespan of mice. Furthermore, NLRP3 mRNA levels were significantly elevated in the blood of ALS patients compared to healthy controls (p = 0.03). In conclusion, NLRP3 could be involved in skeletal muscle pathogenesis of ALS, either through inflammasome or independently, and may play a dual role during disease progression. NLRP3 gene expression levels could be used as a biomarker to improve diagnosis and prognosis in skeletal muscle from animal models and also to support diagnosis in clinical practice with the blood of ALS patients.

Idioma: Inglés

DOI: 10.3390/ijms22052523

Año: 2021

Publicado en: International Journal of Molecular Sciences 22, 5 (2021), 2523 [15 pp.]
ISSN: 1661-6596

Factor impacto JCR: 6.208 (2021)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 69 / 297 = 0.232 (2021) - Q1 - T1
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 50 / 179 = 0.279 (2021) - Q2 - T1

Factor impacto CITESCORE: 6.9 - Computer Science (Q1) - Chemical Engineering (Q1) - Medicine (Q1) - Biochemistry, Genetics and Molecular Biology (Q2)

Factor impacto SCIMAGO: 1.176 - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Organic Chemistry (Q1) - Physical and Theoretical Chemistry (Q1) - Molecular Biology (Q1)

Financiación: info:eu-repo/grantAgreement/ES/FIS-FEDER/PI17-00949
Financiación: info:eu-repo/grantAgreement/ES/UZ/2018-BIO-03

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Área Farmacología (Dpto. Farmac.Fisiol.y Med.L.F.)