title: Differential involvement of optineurin in amyotrophic lateral sclerosis with or without SOD1 mutations.
abstract: BACKGROUND
  Mutations in optineurin have recently been linked to amyotrophic lateral sclerosis (ALS).
  
  
  OBJECTIVE
  To determine whether optineurin-positive skeinlike inclusions are a common pathologic feature in ALS, including SOD1 -linked ALS.
  
  
  METHODS
  Clinical case series.
  
  
  METHODS
  Academic referral center.
  
  
  METHODS
  We analyzed spinal cord sections from 46 clinically and pathologically diagnosed ALS cases and ALS transgenic mouse models overexpressing ALS-linked SOD1 mutations G93A or L126Z.
  
  
  RESULTS
  We observed optineurin-immunoreactive skeinlike inclusions in all the sporadic ALS and familial ALS cases without SOD1 mutation, but not in cases with SOD1 mutations or in transgenic mice overexpressing the ALS-linked SOD1 mutations G93A or L126Z.
  
  
  CONCLUSIONS
  The data from this study provide evidence that optineurin is involved in the pathogenesis of sporadic ALS and non- SOD1 familial ALS, thus supporting the hypothesis that these forms of ALS share a pathway that is distinct from that of SOD1-linked ALS.
authors.affiliation: Division of Neuromuscular Medicine, Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. h-deng@northwestern.edu
authors.forename: Han-Xiang
authors.initials: HX
authors.lastname: Deng
authors.forename: Eileen H
authors.initials: EH
authors.lastname: Bigio
authors.forename: Hong
authors.initials: H
authors.lastname: Zhai
authors.forename: Faisal
authors.initials: F
authors.lastname: Fecto
authors.forename: Kaouther
authors.initials: K
authors.lastname: Ajroud
authors.forename: Yong
authors.initials: Y
authors.lastname: Shi
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yan
authors.forename: Manjari
authors.initials: M
authors.lastname: Mishra
authors.forename: Senda
authors.initials: S
authors.lastname: Ajroud-Driss
authors.forename: Scott
authors.initials: S
authors.lastname: Heller
authors.forename: Robert
authors.initials: R
authors.lastname: Sufit
authors.forename: Nailah
authors.initials: N
authors.lastname: Siddique
authors.forename: Enrico
authors.initials: E
authors.lastname: Mugnaini
authors.forename: Teepu
authors.initials: T
authors.lastname: Siddique
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D018797:Cell Cycle Proteins; D003937:Diagnosis, Differential; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D026901:Membrane Transport Proteins; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D035582:Transcription Factor TFIIIA / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D005136:Eye Proteins; D005819:Genetic Markers; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; C501288:Optn protein, mouse; C000606290:SOD1 protein, human; D035582:Transcription Factor TFIIIA; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1