Mitochondrial medicine for aging and neurodegenerative diseases

Neuromolecular Med. 2008;10(4):291-315. doi: 10.1007/s12017-008-8044-z. Epub 2008 Jun 20.

Abstract

Mitochondria are key cytoplasmic organelles, responsible for generating cellular energy, regulating intracellular calcium levels, altering the reduction-oxidation potential of cells, and regulating cell death. Increasing evidence suggests that mitochondria play a central role in aging and in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Freidriech ataxia. Further, several lines of evidence suggest that mitochondrial dysfunction is an early event in most late-onset neurodegenerative diseases. Biochemical and animal model studies of inherited neurodegenerative diseases have revealed that mutant proteins of these diseases are associated with mitochondria. Mutant proteins are reported to block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins and disrupt the electron transport chain, induce free radicals, cause mitochondrial dysfunction, and, ultimately, damage neurons. This article discusses critical issues of mitochondria causing dysfunction in aging and neurodegenerative diseases, and discusses the potential of developing mitochondrial medicine, particularly mitochondrially targeted antioxidants, to treat aging and neurodegenerative diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / drug effects*
  • Aging / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Energy Metabolism / physiology
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mitochondrial Diseases / drug therapy*
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / physiopathology
  • Mitochondrial Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / toxicity
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / physiology

Substances

  • Antioxidants
  • Mitochondrial Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents