Mitochondria as a therapeutic target for aging and neurodegenerative diseases

Curr Alzheimer Res. 2011 Jun;8(4):393-409. doi: 10.2174/156720511795745401.

Abstract

Mitochondria are cytoplasmic organelles responsible for life and death. Extensive evidence from animal models, postmortem brain studies of and clinical studies of aging and neurodegenerative diseases suggests that mitochondrial function is defective in aging and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Several lines of research suggest that mitochondrial abnormalities, including defects in oxidative phosphorylation, increased accumulation of mitochondrial DNA defects, impaired calcium influx, accumulation of mutant proteins in mitochondria, and mitochondrial membrane potential dissipation are important cellular changes in both early and late-onset neurodegenerative diseases. Further, emerging evidence suggests that structural changes in mitochondria, including increased mitochondrial fragmentation and decreased mitochondrial fusion, are critical factors associated with mitochondrial dysfunction and cell death in aging and neurodegenerative diseases. This paper discusses research that elucidates features of mitochondria that are associated with cellular dysfunction in aging and neurodegenerative diseases and discusses mitochondrial structural and functional changes, and abnormal mitochondrial dynamics in neurodegenerative diseases. It also outlines mitochondria-targeted therapeutics in neurodegenerative diseases.

Publication types

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

MeSH terms

  • Aging / pathology
  • Aging / physiology
  • Animals
  • Brain / ultrastructure*
  • DNA, Mitochondrial / physiology*
  • Humans
  • Mitochondria / pathology*
  • Mitochondrial Diseases / etiology*
  • Models, Biological
  • Neurodegenerative Diseases / complications*
  • Neurodegenerative Diseases / pathology

Substances

  • DNA, Mitochondrial