title: Smads as muscle biomarkers in amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  To identify molecular signatures in muscle from patients with amyotrophic lateral sclerosis (ALS) that could provide insight into the disease process and serve as biomarkers.
  
  
  METHODS
  RNA sequencing was performed on ALS and control muscle samples to identify Smad family members as potential markers of disease. Validation studies were performed in a cohort of 27 ALS patients and 33 controls. The markers were assessed in the G93A superoxide dismutase (SOD)1 mouse at different stages of disease and in a model of sciatic nerve injury.
  
  
  RESULTS
  Smad8, and to a lesser extent Smad1 and 5, mRNAs were significantly elevated in human ALS muscle samples. The markers displayed a remarkably similar pattern in the G93A SOD1 mouse model of ALS with increases detected at preclinical stages. Expression at the RNA and protein levels as well as protein activation (phosphorylation) significantly increased with disease progression in the mouse. The markers were also elevated to a lesser degree in gastrocnemius muscle following sciatic nerve injury, but then reverted to baseline during the muscle reinnervation phase.
  
  
  CONCLUSIONS
  These data indicate that Smad1, 5, 8 mRNA and protein levels, as well as Smad phosphorylation, are elevated in ALS muscle and could potentially serve as markers of disease progression or regression.
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Ying
authors.initials: Y
authors.lastname: Si
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Soojin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Robert
authors.initials: R
authors.lastname: Wians
authors.affiliation: Department of Psychology, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Robert
authors.initials: R
authors.lastname: Sorge
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL ; Birmingham VA Medical Center Birmingham, AL, 35294.
authors.forename: Shin J
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Thaddeus
authors.initials: T
authors.lastname: Kwan
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Mohammad
authors.initials: M
authors.lastname: AlSharabati
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL ; Birmingham VA Medical Center Birmingham, AL, 35294.
authors.forename: Liang
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Gwen
authors.initials: G
authors.lastname: Claussen
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Tina
authors.initials: T
authors.lastname: Anderson
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Dylan
authors.initials: D
authors.lastname: Morgan
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Kazamel
authors.affiliation: Department of Neurology, University of Alabama at Birmingham Birmingham, AL ; Birmingham VA Medical Center Birmingham, AL, 35294 ; Department of Genetics, University of Alabama at Birmingham Birmingham, AL ; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham Birmingham, AL.
authors.forename: Peter H
authors.initials: PH
authors.lastname: King