The Neuroprotective Effect of L-Carnitine against Glyceraldehyde-Induced Metabolic Impairment: Possible Implications in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive regression and memory loss. Dysfunctions of both glucose metabolism and mitochondrial dynamics have been recognized as the main upstream events of the degenerative processes leading to AD. It has been recently found that correcting cell metabolism by providing alternative substrates can prevent neuronal injury by retaining mitochondrial function and reducing AD marker levels. Here, we induced an AD-like phenotype by using the glycolysis inhibitor glyceraldehyde (GA) and explored whether L-carnitine (4-N-trimethylamino-3-hydroxybutyric acid, LC) could mitigate neuronal damage, both in SH-SY5Y neuroblastoma cells and in rat primary cortical neurons. We have already reported that GA significantly modified AD marker levels; here we demonstrated that GA dramatically compromised cellular bioenergetic status, as revealed by glycolysis and oxygen consumption rate (OCR) evaluation. We found that LC ameliorated cell survival, improved OCR and ATP synthesis, prevented the loss of the mitochondrial membrane potential (Δψm) and reduced the formation of reactive oxygen species (ROS). Of note, the beneficial effect of LC did not rely on the glycolytic pathway rescue. Finally, we noticed that LC significantly reduced the increase in pTau levels induced by GA. Overall, these findings suggest that the use of LC can promote cell survival in the setting of the metabolic impairments commonly observed in AD. Our data suggest that LC may act by maintaining mitochondrial function and by reducing the pTau level.

The Role of l-Carnitine in Mitochondria, Prevention of Metabolic Inflexibility and Disease Initiation

“…In addition to carnitines, a number of metabolically active compounds like nicotinamide, thiamine, riboflavin, creatine, and coenzyme Q10 acting at the mitochondrial level have been shown to counteract neuronal damage in conditions of ischemia, hypoxia, and metabolic compromise [ 85 , 86 ].…”

Mitochondrial Dysfunction and Neurodegenerative Disorders: Role of Nutritional Supplementation

“…A meta-analysis by Montgomery et al [ 87 ] confirmed the efficacy of acetyl- l -carnitine for the treatment of mild cognitive impairment and mild Alzheimer’s disease. l -carnitine or acetyl- l -carnitine have been shown to improve manifestations of AD in animal models [ 88 , 89 ]. Kepka et al [ 90 ] have reviewed the potential role of dietary l -carnitine in the prevention of Alzheimer’s disease.…”

Taurine Stabilizing Effect on Lysozyme

“…The human neuroblastoma cell line SH-SY5Y was obtained from American Type Culture Collection (CRL-2266). SH-SY5Y cells were cultured as a monolayer and grown in polystyrene dishes (100 mm diameter) in Dulbecco's Modified Eagle's Medium (DMEM; Corning, New York, NY, USA) supplemented with 10% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 µg/mL streptomycin (Corning, New York, NY, USA) and were maintained in a humidified incubator at 37 • C in a 5% CO 2 atmosphere [50]. To assess the effect of lysozyme fibrils on their survival, SH-SY5Y neuroblastoma cells were plated on 12well plates and, after 24 h, the different types of fibrils where added at a final concentration of 20 µM.…”

“…Briefly, at the end of the experimental procedure, the cells were incubated with 0.5 mL of MTT solution (0.5 g L −1 in PBS) in the dark at 37 • C and a 5% CO 2 atmosphere, in a humidified incubator. After 1 h, the cells were washed with PBS, and the produced formazan crystals were dissolved in 0.5 mL of DMSO [50,52,53]. A decrease in mitochondrial activity resulted in a reduction in the amount of formazan produced and therefore in the absorbance value.…”