ABSTRACT

Introduction...................................................................................................... 476 a-Lipoic Acid: A Mitochondrial Nutrient? ..................................................... 476 Mitochondrial Dysfunction: A Consequence of Aging? ................................. 477 Age-Associated Cognitive Dysfunction and Neurodegenerative Diseases: Prevention and Amelioration by LA?.......................................................... 478

Improving Mitochondrial Function and Reducing Oxidative Damage: Possible Mechanisms of LA on Cognition? ................................................ 479

Combination of LA and Other Mitochondrial Nutrients or Compounds: More Effective than LA Alone in Improving Cognitive Function?............ 481

LA Derivatives: More Potent than LA for Treating Neurodegenerative Diseases?....................................................................... 486

Conclusion ....................................................................................................... 487 Acknowledgments............................................................................................ 487 References ........................................................................................................ 487

Cognitive function declines with age. Increasing evidence shows that mitochondrial dysfunction due to the oxidation of lipids, proteins, and nucleic acids plays an important role in brain aging and age-related neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis, and Huntington’s disease. Mitochondrial decay may be a principal underlying event in aging, including brain aging (Ames et al., 1993; Shigenaga et al., 1994; Ames et al., 1995; Beckman and Ames, 1998; Harman, 2002; Ames, 2003; Roubertoux et al., 2003) and is also associated withwith the onset and development of neurodegenerative diseases (Beal, 1992; Tritschler et al., 1994; Liu and Mori, 1999; Albers and Beal, 2000; Perry et al., 2000; Aliev et al., 2002; Rao and Balachandran, 2002).