Mitochondria and Neurodegeneration

  1. Derek J. Chadwick Organizer and
  2. Jamie Goode
  1. M. Flint Beal

Published Online: 20 MAY 2008

DOI: 10.1002/9780470725207.ch13

Mitochondrial Biology: New Perspectives: Novartis Foundation Symposium 287

Mitochondrial Biology: New Perspectives: Novartis Foundation Symposium 287

How to Cite

Beal, M. F. (2007) Mitochondria and Neurodegeneration, in Mitochondrial Biology: New Perspectives: Novartis Foundation Symposium 287 (eds D. J. Chadwick and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470725207.ch13

Author Information

  1. Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, Room F610, New York, NY 10021, USA

Publication History

  1. Published Online: 20 MAY 2008
  2. Published Print: 5 OCT 2007

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470066577

Online ISBN: 9780470725207

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Keywords:

  • mitochondrial dysfunction and neurodegeneration;
  • cytochrome oxidase-deficient neurons;
  • senile plaques;
  • endoplasmic reticulum;
  • mitochondrial biogenesis and respiration

Summary

There is increasing evidence linking mitochondrial dysfunction to neurodegenerative diseases. Mitochondria are critical regulators of cell death, a key feature of neurodegeneration. Mutations in mitochondrial DNA and oxidative stress both contribute to ageing, which is the greatest risk factor for neurodegenerative diseases. This is the case in Alzheimer's disease, in which there is evidence that both β-amyloid and the amyloid precursor protein may directly interact with mitochondria, leading to increased free radical production. In the case of Huntington's disease (HD), recent evidence suggests that the coactivator PGC1α, a key regulator of mitochondrial biogenesis in respiration, is down-regulated in patients with HD and in several animal models of this neurodegenerative disorder. In Parkinson's disease, the autosomal recessive genes parkin, DJ1 and PINK1 are all linked to either oxidative stress or mitochondrial dysfunction. In amyotrophic lateral sclerosis, there is strong evidence that mutant superoxide dismutase directly interacts with the outer mitochondrial membrane as well as the intermembrane space and matrix. Therefore, an impressive number of disease specific proteins interact with mitochondria. Therapies that target basic mitochondrial processes such as energy metabolism in free radical generation, or specific interactions of diseaserelated protein with mitochondria, hold great promise.