Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative disease

  • David S. Albers
  • M. Flint Beal
Conference paper


A major risk factor for neurodegenerative diseases such as Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP) is aging. Two processes that have been implicated in aging are free radical-induced oxidative damage and mitochondrial dysfunction. A progressive impairment of mitochondrial function and/or increased oxidative damage has been suggested to play critical roles in the pathogenesis of these neurodegenerative diseases. For example, decreased complex I activity, increased oxidative damage and altered activities of antioxidant defense enzymes have been demonstrated in PD. In AD, decrements in complex IV activity and increased oxidative damage have been reported. Reductions in complex II activity, increased cortical lactate levels and oxidative damage have been described in HD. Some familial ALS cases are associated with mutations in the gene for Cu,Zn superoxide dismutase (SOD1) while increased oxidative damage is observed in sporadic ALS. Studies in PSP have demonstrated regionally specific reductions in brain and muscle mitochondrial function, hypofrontality and increased oxidative damage. Altogether, the age-dependent onset and progressive course of these neurodegenerative diseases may ultimately highlight an association between aging, mitochondrial impairment and oxidative stress.


Amyotrophic Lateral Sclerosis Progressive Supranuclear Palsy Progressive Supranuclear Palsy Familial Amyotrophic Lateral Sclerosis Progressive Supranuclear Palsy Patient 
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Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • David S. Albers
    • 2
  • M. Flint Beal
    • 1
  1. 1.Department of Neurology and NeuroscienceWeill Medical College of Cornell UniversityNew YorkUSA
  2. 2.Department of Neurology and Neuroscience, Room A-503Weill Medical College of Cornell UniversityNew YorkUSA

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