NeuroMolecular Medicine

, Volume 10, Issue 4, pp 291–315

Mitochondrial Medicine for Aging and Neurodegenerative Diseases

Review Paper

DOI: 10.1007/s12017-008-8044-z

Cite this article as:
Reddy, P.H. Neuromol Med (2008) 10: 291. doi:10.1007/s12017-008-8044-z

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 betaAlzheimer's diseaseAmyotrophic lateral sclerosisAmyloid precursor proteinAdenosine triphosphateCaloric restrictedElectron transport chainFRDAFreidriech ataxiaHydrogen peroxideHuntington's diseaseMitochondrial DNAPeroxisome proliferator activated receptor–coactivatorSuperoxide radicalOxidative phosphorylationParkinson's diseaseReactive oxygen speciesSS 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

Copyright information

© Humana Press 2008

Authors and Affiliations

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