Alterations of signaling pathways in muscle tissues of patients with amyotrophic lateral sclerosis



Introduction: Amyotrophic lateral sclerosis (ALS), a degenerative disorder of the central nervous system, manifests as progressive weakening of muscles. The diagnosis and prognosis of ALS are often unclear, so useful biomarkers are needed. Methods: Total proteins were extracted from muscle samples from 36 ALS, 17 spinal muscular atrophy (SMA), and 36 normal individuals. The expression levels of 134 proteins and phosphoproteins were assessed using protein pathway array analysis. Results: Seventeen proteins were differentially expressed between ALS and normal muscle, and 9 proteins were differentially expressed between ALS and SMA muscle. The low-level expression of Akt and Factor XIIIB correlates with unfavorable survival, and the risk score calculated based on these proteins predicts the survival of each individual patient. Conclusions: Some proteins could be selected as clinically useful biomarkers. Specifically, Akt and Factor XIIIB were found to be promising biomarkers for estimating prognosis in ALS. Muscle Nerve, 2012