Circulating miR-223/NLRP3 axis and IL-1β level in functional disease progression of amyotrophic lateral sclerosis.

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease identified by progressive motor neuron loss. NLRP3 inflammasomes induce inflammation and pyroptosis, which can lead to neurodegeneration, muscle atrophy, and respiratory decline. miR-223 targets NLRP3 and suppresses inflammasome formation. Here, miR-223, NLRP3 and IL-1β levels were evaluated as plasma biomarkers in the incidence and progression of ALS.

Methods: 32 ALS patients and 32 healthy subjects were assessed. In all patients, the functional disability was determined by Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and the respiratory dysfunction was assessed by the percent predicted forced vital capacity (ppFVC) index in spirometry examination. Plasma levels of miR-223, NLRP3 and IL-1β were assessed in ALS and control groups.

Results: Compared to the healthy controls, ALS patients showed decreased miR-223 expression (P < 0.0001), increased NLRP3 expression (P = 0.0002) and increased IL-1β level (P = 0.0003). The areas under the ROC curves for miR-223, NLRP3 and IL-1β were 0.82, 0.76 and 0.75 respectively. The ALSFRS-R and ppFVC values were positively correlated with miR-223 and negatively correlated with NLRP3 and IL-1β levels.

Conclusion: Our results indicated that changes in miR-223, NLRP3 and IL-1β levels may correlate with the occurrence and functional progression of ALS. Additionally, therapeutic approaches based on miR-223 and inflammatory mediators can be proposed as effective strategies against disease progression.