NeuroMolecular Medicine

, Volume 10, Issue 4, pp 291–315 | Cite as

Mitochondrial Medicine for Aging and Neurodegenerative Diseases

Review Paper

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.

Keywords

Amyloid beta Alzheimer's disease Amyotrophic lateral sclerosis Amyloid precursor protein Adenosine triphosphate Caloric restricted Electron transport chain FRDA Freidriech ataxia Hydrogen peroxide Huntington's disease Mitochondrial DNA Peroxisome proliferator activated receptor–coactivator Superoxide radical Oxidative phosphorylation Parkinson's disease Reactive oxygen species SS peptide 

Abbreviations

Amyloid beta

AD

Alzheimer’s disease

ALS

Amyotrophic lateral sclerosis

APP

Amyloid precursor protein

ATP

Adenosine triphosphate

CR

Caloric restricted

ETC

Electron transport chain

FRDA

Freidriech ataxia

H2O2

Hydrogen peroxide

HD

Huntington’s disease

mtDNA

Mitochondrial DNA

PGC-1α

Peroxisome proliferator-activated receptor- coactivator

O2

Superoxide radical

OXPHOS

Oxidative phosphorylation

PD

Parkinson’s disease

ROS

Reactive oxygen species

SS peptide

Szeto-Schiller peptide

Notes

Acknowledgments

I sincerely thank Drs. Maria Manczak and Wei Zhao (postdoctoral scientists in the lab) for their technical assistance of MitoQ and SS-31 treatments of N2a cells. The research presented in this article was supported by grants from the American Federation for Aging Research, National Institutes of Health (AG028072 and AG026051), and KaloBios Pharmaceuticals, Inc.

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Copyright information

© Humana Press 2008

Authors and Affiliations

  1. 1.Neurogenetics Laboratory, Neurological Sciences InstituteOregon Health & Science UniversityBeavertonUSA

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