Reducing mitochondrial decay with mitochondrial nutrients to delay and treat cognitive dysfunction, Alzheimer's disease, and Parkinson's disease

Abstract

Mitochondrial decay due to oxidative damage is a contributor to brain aging and age-related neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). One type of mitochondrial decay is oxidative modification of key mitochondrial enzymes. Enzyme dysfunction, that is due to poor binding of substrates and coenzymes may be ameliorated by supplementing adequate levels of substrates or coenzyme precursors. Such supplementation with mitochondrial nutrients (mt-nutrients) may be useful to prevent or delay mitochondrial decay, thus prevent or treat AD and PD. In the present review, we survey the literature to identify mt-nutrients that can (1) protect mitochondrial enzymes and/or stimulate enzyme activity by elevating levels of substrates and cofactors; (2) induce phase-2 enzymes to enhance antioxidant defenses; (3) scavenge free radicals and prevent oxidant production in mitochondria, and (4) repair mitochondrial membrane. Then, we discuss the relationships among mt-nutrient deficiency, mitochondrial decay, and cognitive dysfunction, and summarize available evidence suggesting an effect of mt-nutrient supplementation on AD and PD. It appears that greater effects might be obtained by longer-term administration of combinations of mt-nutrients. Thus, optimal doses of combinations of mt-nutrients to delay and repair mitochondrial decay could be a strategy for preventing and treating cognitive dysfunction, including AD and PD.

Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells

“…Thus, oxidative damage, destruction of calcium homeostasis and mitochondrial dysfunction are essentially consequences of Glu-induced excitotoxicity. Consistent with these findings, antioxidants and mitochondrial nutrients [8,9] may be promising candidates for the prevention and treatment of these diseases.…”

R-α-Lipoic acid and acetyl-l-carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes

“…The complementary effect of LA and ALC on cognitive and mitochondrial dysfunction has been shown in ageing rats [27,28,40]. One reason is that LA+ALC act on different pathways necessary for mitochondria: LA is a mitochondrial antioxidant and cofactor of pyruvate dehydrogenase, while ALC is an energy enhancer [25,41]. Another possibility is that ALC, although stimulating mitochondrial function, may cause side effects of oxidative stress in mitochondria [42], while LA, an effective mitochondrial antioxidant, is able to ameliorate that side effect of ALC.…”

D-Galactose Induces a Mitochondrial Complex I Deficiency in Mouse Skeletal Muscle: Potential Benefits of Nutrient Combination in Ameliorating Muscle Impairment

“…We assigned these compounds to different groups of mitochondrial nutrients as previously described. 16 Previous studies in rodents have shown that combinations of nutrients have synergistic effects in various metabolic pathways and are more potent than treating the animals with individual nutrients. 48 For example, supplementing mice with lipoic acid, carnitine, and CoQ10 had a more significant beneficial effect on agerelated oxidative stress than individual treatment with these compounds.…”

“…As described in previous publications, 13,15,16 we have identified a group of mitochondria targeting antioxidants and cofactors, which are referred to as ''mitochondrial nutrients.'' With these mitochondrial nutrients, we aim to reverse the mitochondrial dysfunction that occurs during the aging process.…”