Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration.

Autor: Andersen JV; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: jens.andersen@sund.ku.dk., Markussen KH; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY, USA., Jakobsen E; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Schousboe A; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Waagepetersen HS; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Rosenberg PA; Department of Neurology and the F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA; Program in Neuroscience, Harvard Medical School, Boston, MA, USA., Aldana BI; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: blanca.aldana@sund.ku.dk.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2021 Sep 15; Vol. 196, pp. 108719. Date of Electronic Publication: 2021 Jul 15.
DOI: 10.1016/j.neuropharm.2021.108719
Abstrakt: Glutamate is the primary excitatory neurotransmitter of the brain. Cellular homeostasis of glutamate is of paramount importance for normal brain function and relies on an intricate metabolic collaboration between neurons and astrocytes. Glutamate is extensively recycled between neurons and astrocytes in a process known as the glutamate-glutamine cycle. The recycling of glutamate is closely linked to brain energy metabolism and is essential to sustain glutamatergic neurotransmission. However, a considerable amount of glutamate is also metabolized and serves as a metabolic hub connecting glucose and amino acid metabolism in both neurons and astrocytes. Disruptions in glutamate clearance, leading to neuronal overstimulation and excitotoxicity, have been implicated in several neurodegenerative diseases. Furthermore, the link between brain energy homeostasis and glutamate metabolism is gaining attention in several neurological conditions. In this review, we provide an overview of the dynamics of synaptic glutamate homeostasis and the underlying metabolic processes with a cellular focus on neurons and astrocytes. In particular, we review the recently discovered role of neuronal glutamate uptake in synaptic glutamate homeostasis and discuss current advances in cellular glutamate metabolism in the context of Alzheimer's disease and Huntington's disease. Understanding the intricate regulation of glutamate-dependent metabolic processes at the synapse will not only increase our insight into the metabolic mechanisms of glutamate homeostasis, but may reveal new metabolic targets to ameliorate neurodegeneration.
(Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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