l-Serine links metabolism with neurotransmission
| Autor: | Pierre-Antoine Vigneron, Marianne Maugard, Gilles Bonvento, Juan P. Bolaños |
|---|---|
| Přispěvatelé: | Agence Nationale de la Recherche (France), French National Foundation on Alzheimer’s Disease and Related Disorders, Fondation pour la Recherche Médicale, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Junta de Castilla y León, Fundación Ramón Areces, Fundación BBVA |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Phosphorylated pathwayphos D-serine Oxidative phosphorylation Synaptic Transmission Synaptic plasticity 03 medical and health sciences Adenosine Triphosphate 0302 clinical medicine Serine Glycolysis Chemistry General Neuroscience Metabolism Metabolic pathway Glucose 030104 developmental biology Phoglycerate dehydrogenase Astrocytes Phosphorylation Energy Metabolism Neuroglia Flux (metabolism) Neuroscience 030217 neurology & neurosurgery Homeostasis |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 2017-0637 |
| Popis: | Brain energy metabolism is often considered as a succession of biochemical steps that metabolize the fuel (glucose and oxygen) for the unique purpose of providing sufficient ATP to maintain the huge information processing power of the brain. However, a significant fraction (10–15 %) of glucose is shunted away from the ATP-producing pathway (oxidative phosphorylation) and may be used to support other functions. Recent studies have pointed to the marked compartmentation of energy metabolic pathways between neurons and glial cells. Here, we focused our attention on the biosynthesis of l-serine, a non-essential amino acid that is formed exclusively in glial cells (mostly astrocytes) by re-routing the metabolic fate of the glycolytic intermediate, 3-phosphoglycerate (3PG). This metabolic pathway is called the phosphorylated pathway and transforms 3PG into l-serine via three enzymatic reactions. We first compiled the available data on the mechanisms that regulate the flux through this metabolic pathway. We then reviewed the current evidence that is beginning to unravel the roles of l-serine both in the healthy and diseased brain, leading to the notion that this specific metabolic pathway connects glial metabolism with synaptic activity and plasticity. We finally suggest that restoring astrocyte-mediated l-serine homeostasis may provide new therapeutic strategies for brain disorders. This work was supported by grants from the Agence Nationale de la Recherche (ANR 2011MALZ-0003 to GB), Association France Alzheimer and Fondation de France (Prix Spécial 2012 to GB), Fondation Plan Alzheimer (GB), Infrastructure de Recherche translationnelle pour les Biothérapies en Neurosciences-NeurATRIS ANR-11-INBS-0011 (GB). PAV is a recipient of a PhD fellowship from the Fondation pour la Recherche Médicale (FRM grant number ECO20170637547). Juan P. Bolanos is funded by MCINU (PID2019-105699RB-I00/ AEI / 10.13039/501100011033 and RED2018-102576-T), Instituto de Salud Carlos III (RD12/0043/0021), Junta de Castilla y León (Escalera de Excelencia CLU-2017-03), Ayudas Equipos Investigación Biomedicina 2017 Fundación BBVA, and Fundación Ramón Areces. |
| Databáze: | OpenAIRE |
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