Mitochondria, free radicals, and neurodegeneration

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Abstract

A central role for defective mitochondrial energy production, and the resulting increased levels of free radicals, in the pathogenesis of various neurodegenerative diseases is gaining increasing acceptance. Defects in energy metabolism may contribute to both excitotoxicity and oxidative damage. Evidence implicating energy defects in neurodegenerative diseases comes from similarities to known mitochondrial disorders, including delayed and variable age of onset, slow progression, and symmetric degeneration of circumscribed groups of neurons.

References (45)

  • LL Dugan et al.

    Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-d-aspartate

    J Neurosci

    (1995)
  • U Reynolds et al.

    Glutamate induces the production of reactive oxygen species in cultured forebrain neurons following NMDA receptor activation

    J Neurosci

    (1995)
  • M Patel et al.

    Requirement for superoxide in excitotoxic cell death

    Neuron

    (1996)
  • VL Dawson et al.

    Resistance to neurotoxicity in cortical cultures from neuronal nitric oxide synthase-deficient mice

    J Neurosci

    (1996)
  • JB Schulz et al.

    Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo

    J Neurosci

    (1995)
  • JB Schulz et al.

    Striatal malonate lesions are attenuated in neuronal nitric oxide knockout mice

    J Neurochem

    (1996)
  • C Szabo et al.

    DNA strand breakage, activation of poly(ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity in macrophages and smooth muscle cells exposed to peroxynitrite

    Proc Natl Acad Sci USA

    (1996)
  • DR Rosen et al.

    Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis

    Nature

    (1993)
  • RH Brown

    Amyotrophic lateral sclerosis: recent insights from genetics and transgenic mice

    Cell

    (1995)
  • ME Ripps et al.

    Transgenic mice expressing an altered murine superoxide dismutase gene provide an animal model of amyotrophic lateral sclerosis

    Proc Natl Acad Sci USA

    (1995)
  • PC Wong et al.

    An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria

    Neuron

    (1995)
  • P-H Tu et al.

    Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions

    Proc Natl Acad Sci USA

    (1996)
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