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Mitochondrial Medicine for Aging and Neurodegenerative Diseases

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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.

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Abbreviations

Aß:

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

O •2 − :

Superoxide radical

OXPHOS:

Oxidative phosphorylation

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

SS peptide:

Szeto-Schiller peptide

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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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  1. Neurogenetics Laboratory, Neurological Sciences Institute, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR, 97006, USA

    P. Hemachandra Reddy

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Reddy, P.H. Mitochondrial Medicine for Aging and Neurodegenerative Diseases. Neuromol Med 10, 291–315 (2008). https://doi.org/10.1007/s12017-008-8044-z

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