The Effects and Mechanisms of Mitochondrial Nutrient α-Lipoic Acid on Improving Age-Associated Mitochondrial and Cognitive Dysfunction: An Overview
- 29 June 2007
- journal article
- review article
- Published by Springer Science and Business Media LLC in Neurochemical Research
- Vol. 33 (1), 194-203
- https://doi.org/10.1007/s11064-007-9403-0
Abstract
We have identified a group of nutrients that can directly or indirectly protect mitochondria from oxidative damage and improve mitochondrial function and named them "mitochondrial nutrients". The direct protection includes preventing the generation of oxidants, scavenging free radicals or inhibiting oxidant reactivity, and elevating cofactors of defective mitochondrial enzymes with increased Michaelis-Menten constant to stimulate enzyme activity, and also protect enzymes from further oxidation, and the indirect protection includes repairing oxidative damage by enhancing antioxidant defense systems either through activation of phase 2 enzymes or through increase in mitochondrial biogenesis. In this review, we take alpha-lipoic acid (LA) as an example of mitochondrial nutrients by summarizing the protective effects and possible mechanisms of LA and its derivatives on age-associated cognitive and mitochondrial dysfunction of the brain. LA and its derivatives improve the age-associated decline of memory, improve mitochondrial structure and function, inhibit the age-associated increase of oxidative damage, elevate the levels of antioxidants, and restore the activity of key enzymes. In addition, co-administration of LA with other mitochondrial nutrients, such as acetyl-L: -carnitine and coenzyme Q10, appears more effective in improving cognitive dysfunction and reducing oxidative mitochondrial dysfunction. Therefore, administrating mitochondrial nutrients, such as LA and its derivatives in combination with other mitochondrial nutrients to aged people and patients suffering from neurodegenerative diseases, may be an effective strategy for improving mitochondrial and cognitive dysfunction.Keywords
This publication has 98 references indexed in Scilit:
- Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's diseaseNeurobiology of Aging, 2008
- Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger protection by cotreatment of acetyl-L-carnitine and α-lipoic acid against HNE-mediated oxidative stress and neurotoxicity: Implications for Alzheimer's diseaseFree Radical Biology & Medicine, 2007
- The role of AMP‐activated protein kinase in mitochondrial biogenesisJournal Of Physiology-London, 2006
- Chronic systemic D‐galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: Protective effects of R‐α‐lipoic acidJournal of Neuroscience Research, 2006
- Effect of alpha-lipoic acid supplementation on markers of protein oxidation in post-mitotic tissues of ageing ratCell Biochemistry and Function, 2005
- Mitochondrial DNA modifies cognition in interaction with the nuclear genome and age in miceNature Genetics, 2003
- The antioxidants α‐lipoic acid and N‐acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 miceJournal of Neurochemistry, 2003
- Nutritional approaches to combat oxidative stress in Alzheimer’s diseaseThe Journal of Nutritional Biochemistry, 2002
- Beneficial effects of α-lipoic acid plus vitamin E on neurological deficit, reactive gliosis and neuronal remodeling in the penumbra of the ischemic rat brainNeuroscience Letters, 2002
- Effect of aging and acetyl-l-carnitine on the activity of cytochrome oxidase and adenine nucleotide translocase in rat heart mitochondriaFEBS Letters, 1994