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.

• Authors: Simona Magi, Alessandra Preziuso, Silvia Piccirillo, Francesca Giampieri, Danila Cianciosi, Monia Orciani, Salvatore Amoroso
• Journal: Cells (Cells) Vol. 10 Issue 8 (08 17 2021) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 34440878 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MAPT protein, human
• Neuroprotective Agents
• Reactive Oxygen Species
• tau Proteins
• Glyceraldehyde
• Adenosine Triphosphate
• Carnitine

Topics

• Adenosine Triphosphate (biosynthesis)
• Alzheimer Disease (chemically induced, metabolism)
• Animals
• Carnitine (pharmacology)
• Cell Survival (drug effects)
• Glyceraldehyde (toxicity)
• Glycolysis
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Models, Biological
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Oxygen Consumption (drug effects)
• Phosphorylation (drug effects)
• Rats
• Reactive Oxygen Species (metabolism)
• tau Proteins (metabolism)