Modulation of lipid peroxidation and mitochondrial function improves neuropathology in Huntington's disease mice Academic Article uri icon


MeSH Major

  • Huntington Disease
  • Lipid Peroxidation
  • Mitochondria
  • Neostriatum


  • Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Oxidative damage has been associated with pathological neuronal loss in HD. The therapeutic modulation of oxidative stress and mitochondrial function using low molecular weight compounds may be an important strategy for delaying the onset and slowing the progression of HD. In the present study, we found a marked increase of 4-hydroxy-2-nonenal (4-HNE) adducts, a lipid peroxidation marker, in the caudate and putamen of HD brains and in the striatum of HD mice. Notably, 4-HNE immunoreactivity was colocalized with mutant huntingtin inclusions in the striatal neurons of R6/2 HD mice. Administration of nordihydroguaiaretic acid (NDGA), an antioxidant that functions by inhibiting lipid peroxidation, markedly reduced 4-HNE adduct formation in the nuclear inclusions of R6/2 striatal neurons. NDGA also protected cultured neurons against oxidative stress-induced cell death by improving ATP generation and mitochondrial morphology and function. In addition, NDGA restored mitochondrial membrane potential, mitochondrial structure, and synapse structure in the striatum of R6/2 mice and increased their lifespan. The present findings suggest that further therapeutic studies using NDGA are warranted in HD and other neurodegenerative diseases characterized by increased oxidative stress and altered mitochondrial function.

publication date

  • April 2011



  • Academic Article



  • eng

PubMed Central ID

  • PMC3151672

Digital Object Identifier (DOI)

  • 10.1007/s00401-010-0788-5

PubMed ID

  • 21161248

Additional Document Info

start page

  • 487

end page

  • 98


  • 121


  • 4