title: PGC-1α protects neurons and alters disease progression in an amyotrophic lateral sclerosis mouse model.
abstract: BACKGROUND
  Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. We sought to determine whether peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) would have a beneficial effect on this disease.
  
  
  METHODS
  PGC-1α transgenic mice were crossed with SOD1 mutant G93A DL mice.
  
  
  RESULTS
  We observed a moderate but non-significant increase in average lifespan in PGC-1α/G93A DL mice, as compared with G93A DL mice (292 ± 3 days vs. 274 ± 7 days). Although the onset of ALS was not altered, progression of the disease was significantly slower (≈34% increase in duration) in the PGC-1α/G93A DL mice. These mice also exhibited markedly improved performance on the rotarod test, and the improved motor activity was associated with a decreased loss of motor neurons and less degeneration of neuromuscular junctions.
  
  
  CONCLUSIONS
  A sustained level of excitatory amino acid transporter protein 2 (EAAT2) in astrocytes of the PGC-1α/G93A DL mice may contribute to neuronal protection.
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Huiyun
authors.initials: H
authors.lastname: Liang
authors.forename: Walter F
authors.initials: WF
authors.lastname: Ward
authors.forename: Youngmok C
authors.initials: YC
authors.lastname: Jang
authors.forename: Arunabh
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Alex F
authors.initials: AF
authors.lastname: Bokov
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Amanda
authors.initials: A
authors.lastname: Jernigan
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
mesh_terms: D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005998:Glycine / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000409:Alanine; D005998:Glycine