Mitochondrial Decay in the Brains of Old Rats: Ameliorating Effect of Alpha-Lipoic Acid and Acetyl-l-carnitine

Long, Jiangang; Gao, Feng; Tong, Liqi; Cotman, Carl W.; Ames, Bruce N.; Liu, Jiankang

doi:10.1007/s11064-008-9850-2

Cited by 80 publications

(68 citation statements)

References 35 publications

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“…A beneficial effect of the combined action of R-a-lipoic acid and acetyl-L-carnitine (LA/ALC) on mitochondrial functions was demonstrated in brain mitochondria from old rats. These mitochondria had significantly decreased endogenous antioxidant levels and SOD activity and exhibited oxidative damage to lipids and proteins, as well as decreased activities of complex I, IV and V (ATP synthase) [91]. Feeding LA/ALC to old rats partially restored mitochondrial function to that observed in young rats, indicating that nutrients targeting mitochondria could ameliorate mitochondrial decay through prevention of oxidative damage.…”

Section: Creatinementioning

confidence: 92%

Mitochondria as targets for chemotherapy

2009

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Mitochondrial malfunctioning is implicated in the pathogenesis of a variety of disorders, including cancer and multiple neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease. Disturbance of mitochondrial vital functions, e.g., production of ATP, calcium buffering capacity, and generation of reactive oxygen species, can be potentially involved in disease pathogenesis. Neurological disorders caused by mitochondrial deterioration are often associated with cell loss within specific brain regions. In contrast, mitochondrial alterations in tumor cells and the "Warburg effect" might lead to cell survival and resistance of tumor cells to chemotherapy. This review is devoted to the role of mitochondria in neurodegeneration and tumor formation, and describes how targeting of mitochondria can be beneficial in the therapy of these diseases, which affect a large human population.

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Section: Creatinementioning

confidence: 92%

Mitochondria as targets for chemotherapy

2009

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“…Brains were removed on ice and stored at −80°C. For the analysis of complex IV activity (Long et al 2009), assay buffer contained 50 mmol/l phosphate buffer, 0.1% bovine serum albumin, 0.2% Tween-20, and 60 μmol/l reduced cytochrome c. Complex IV was measured by monitoring the decrease of reduced cytochrome C at 550 nm.…”

Section: Brain Mitochondrial Complex IV Activitymentioning

confidence: 99%

A complex dietary supplement augments spatial learning, brain mass, and mitochondrial electron transport chain activity in aging mice

Aksenov

Long

Liu

et al. 2011

AGE

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We developed a complex dietary supplement designed to offset five key mechanisms of aging and tested its effectiveness in ameliorating age-related cognitive decline using a visually cued Morris water maze test. All younger mice (<1 year old) learned the task well. However, older untreated mice (>1 year) were unable to learn the maze even after 5 days, indicative of strong cognitive decline at older ages. In contrast, no cognitive decline was evident in older supplemented mice, even when ∼2 years old. Supplemented older mice were nearly 50% better at locating the platform than age-matched controls. Brain weights of supplemented mice were significantly greater than controls, even at younger ages. Reversal of cognitive decline in activity of complexes III and IV by supplementation was significantly associated with cognitive improvement, implicating energy supply as one possible mechanism. These results represent proof of principle that complex dietary supplements can provide powerful benefits for cognitive function and brain aging.

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“…-Cys. In a previous study, we found a large increase in MDA in brain mitochondria of old rats (0.21 lmol/mg in young vs. 0.42 lmol/mg in old) [20].…”

Section: Introductionmentioning

confidence: 63%

Neuronal Mitochondrial Toxicity of Malondialdehyde: Inhibitory Effects on Respiratory Function and Enzyme Activities in Rat Brain Mitochondria

et al. 2008

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Malondialdehyde (MDA) is a product of oxidative damage to lipids, amino acids and DNA, and accumulates with aging and diseases. MDA can possibly react with amines so as to modify proteins and inactivate enzymes; it can also modify nucleosides so as to cause mutagenicity. Brain mitochondrial dysfunction is a major contributor to aging and neurodegenerative diseases. We hypothesize that MDA accumulated during aging targets mitochondrial enzymes so as to cause further mitochondrial dysfunction and additional contributions to aging and neurodegeneration. Herein, we investigated the neuronal mitochondrial toxic effects of MDA on mitochondrial respiration and activities of enzymes (mitochondrial complexes I-V, alpha-ketoglutarate dehydrogenase (KGDH) and pyruvate dehydrogenase (PDH)), in isolated rat brain mitochondria. MDA depressed mitochondrial membrane potential, and also showed a dose-dependent inhibition of mitochondrial complex I- and complex II-linked respiration. Complex I and II, and PDH activities were depressed by MDA at >or=0.2 micromol/mg; KGDH and complex V were inhibited by >or=0.4 and >or=1.6 micromol MDA/mg, respectively. However, MDA did not have any toxic effects on complex III and IV activities over the range 0-2 micromol/mg. MDA significantly elevated mitochondrial reactive oxygen species (ROS) and protein carbonyls at 0.2 and 0.002 micromol/mg, respectively. As for the antioxidant defense system, a high dose of MDA slightly decreased mitochondrial GSH and superoxide dismutase. These results demonstrate that MDA causes neuronal mitochondrial dysfunction by directly promoting generation of ROS and modifying mitochondrial proteins. The results suggest that MDA-induced neuronal mitochondrial toxicity may be an important contributing factor to brain aging and neurodegenerative diseases.

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Mitochondrial Decay in the Brains of Old Rats: Ameliorating Effect of Alpha-Lipoic Acid and Acetyl-l-carnitine

Cited by 80 publications

References 35 publications

Mitochondria as targets for chemotherapy

Mitochondria as targets for chemotherapy

A complex dietary supplement augments spatial learning, brain mass, and mitochondrial electron transport chain activity in aging mice

Neuronal Mitochondrial Toxicity of Malondialdehyde: Inhibitory Effects on Respiratory Function and Enzyme Activities in Rat Brain Mitochondria

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