Enhancement of L-3-hydroxybutyryl-CoA dehydrogenase activity and circulating ketone body levels by pantethine. Relevance to dopaminergic injury

<p>Abstract</p> <p>Background</p> <p>The administration of the ketone bodies hydroxybutyrate and acetoacetate is known to exert a protective effect against metabolic disorders associated with cerebral pathologies. This suggests that the enhancement of their endogenous production might be a rational therapeutic approach. Ketone bodies are generated by fatty acid beta-oxidation, a process involving a mitochondrial oxido-reductase superfamily, with fatty acid-CoA thioesters as substrates. In this report, emphasis is on the penultimate step of the process, i.e. L-3-hydroxybutyryl-CoA dehydrogenase activity. We determined changes in enzyme activity and in circulating ketone body levels in the MPTP mouse model of Parkinson's disease. Since the active moiety of CoA is pantetheine, mice were treated with pantethine, its naturally-occurring form. Pantethine has the advantage of being known as an anti-inflammatory and hypolipidemic agent with very few side effects.</p> <p>Results</p> <p>We found that dehydrogenase activity and circulating ketone body levels were drastically reduced by the neurotoxin MPTP, whereas treatment with pantethine overcame these adverse effects. Pantethine prevented dopaminergic neuron loss and motility disorders. In vivo and in vitro experiments showed that the protection was associated with enhancement of glutathione (GSH) production as well as restoration of respiratory chain complex I activity and mitochondrial ATP levels. Remarkably, pantethine treatment boosted the circulating ketone body levels in MPTP-intoxicated mice, but not in normal animals.</p> <p>Conclusions</p> <p>These finding demonstrate the feasibility of the enhancement of endogenous ketone body production and provide a promising therapeutic approach to Parkinson's disease as well as, conceivably, to other neurodegenerative disorders.</p

Potential antiviral effects of pantethine against SARS-CoV-2

Abstract SARS-CoV-2 interacts with cellular cholesterol during many stages of its replication cycle. Pantethine was reported to reduce total cholesterol levels and fatty acid synthesis and potentially alter different processes that might be involved in the SARS-CoV-2 replication cycle. Here, we explored the potential antiviral effects of pantethine in two in vitro experimental models of SARS-CoV-2 infection.Pantethine reduced the infection of cells by SARS-CoV-2 in both preinfection and postinfection treatment regimens. Accordingly, cellular expression of the viral spike and nucleocapsid proteins was substantially reduced, and we observed a significant reduction in viral copy numbers in the supernatant of cells treated with pantethine. In addition, pantethine inhibited the infection-induced increase in TMPRSS2 and HECT E3 ligase expression in infected cells as well as the increase in antiviral interferon-beta response and inflammatory gene expression in Calu-3a cells. Our results demonstrate that pantethine, which is well tolerated in humans, was very effective in controlling SARS-CoV-2 infection and might represent a new therapeutic drug that can be repurposed for the prevention or treatment of COVID-19 and long COVID syndrome

Implication des radicaux libres dans le cancer et la pathologie bilharzienne (exploitation des propriétés anti-radiculaires de l'hydrogène moléculaire)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Effets neuroprotecteurs des composés thiol (l'exemple de la pantéthine)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Sur un lieu d'hibernation de la Coccinelle Titthaspis sedecimpunctata dans la région lyonnaise

Legay Jean-Marie, De reggi Max. Sur un lieu d'hibernation de la Coccinelle Titthaspis sedecimpunctata dans la région lyonnaise. In: Bulletin mensuel de la Société linnéenne de Lyon, 31ᵉ année, n°9, novembre 1962. pp. 267-269

Lithostathine, the Presumed Pancreatic Stone Inhibitor, Does Not Interact Specifically with Calcium Carbonate Crystals

International audienc

What function for human lithostathine?: structural investigations by three-dimensional structure modeling and high-resolution NMR spectroscopy

International audienc