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

Research output: Contribution to journal › Review › Research › peer-review

Standard

Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration. / Andersen, Jens V.; Markussen, Kia H.; Jakobsen, Emil; Schousboe, Arne; Waagepetersen, Helle S.; Rosenberg, Paul A.; Aldana, Blanca I.

In: Neuropharmacology, Vol. 196, 108719, 2021.

Research output: Contribution to journal › Review › Research › peer-review

Harvard

Andersen, JV, Markussen, KH, Jakobsen, E, Schousboe, A, Waagepetersen, HS, Rosenberg, PA & Aldana, BI 2021, 'Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration', Neuropharmacology, vol. 196, 108719. https://doi.org/10.1016/j.neuropharm.2021.108719

APA

Andersen, J. V., Markussen, K. H., Jakobsen, E., Schousboe, A., Waagepetersen, H. S., Rosenberg, P. A., & Aldana, B. I. (2021). Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration. Neuropharmacology, 196, [108719]. https://doi.org/10.1016/j.neuropharm.2021.108719

Vancouver

Andersen JV, Markussen KH, Jakobsen E, Schousboe A, Waagepetersen HS, Rosenberg PA et al. Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration. Neuropharmacology. 2021;196. 108719. https://doi.org/10.1016/j.neuropharm.2021.108719

Author

Andersen, Jens V. ; Markussen, Kia H. ; Jakobsen, Emil ; Schousboe, Arne ; Waagepetersen, Helle S. ; Rosenberg, Paul A. ; Aldana, Blanca I. / Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration. In: Neuropharmacology. 2021 ; Vol. 196.

Bibtex

@article{ee90fa13d00b452ea585230a5fa66869,
title = "Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration",
abstract = "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.",
keywords = "Alzheimer's disease (AD), Aspartate aminotransferase (AAT), Glutamate dehydrogenase (GDH), Glutamate-glutamine cycle, Glutamic acid, Huntington's disease (HD), Malate-aspartate shuttle (MAS), Neurotransmitter recycling",
author = "Andersen, {Jens V.} and Markussen, {Kia H.} and Emil Jakobsen and Arne Schousboe and Waagepetersen, {Helle S.} and Rosenberg, {Paul A.} and Aldana, {Blanca I.}",
note = "Funding Information: The Scholarship of Peter & Emma Thomsen is gratefully acknowledged for personal financial support to JVA. PAR was supported by NIH grants NS066019 , MH104318 , EY027881 , HD018655 . Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
doi = "10.1016/j.neuropharm.2021.108719",
language = "English",
volume = "196",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Pergamon Press",

}

RIS

TY - JOUR

T1 - Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration

AU - Andersen, Jens V.

AU - Markussen, Kia H.

AU - Jakobsen, Emil

AU - Schousboe, Arne

AU - Waagepetersen, Helle S.

AU - Rosenberg, Paul A.

AU - Aldana, Blanca I.

N1 - Funding Information: The Scholarship of Peter & Emma Thomsen is gratefully acknowledged for personal financial support to JVA. PAR was supported by NIH grants NS066019 , MH104318 , EY027881 , HD018655 . Publisher Copyright: © 2021 The Authors

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Alzheimer's disease (AD)

KW - Aspartate aminotransferase (AAT)

KW - Glutamate dehydrogenase (GDH)

KW - Glutamate-glutamine cycle

KW - Glutamic acid

KW - Huntington's disease (HD)

KW - Malate-aspartate shuttle (MAS)

KW - Neurotransmitter recycling

U2 - 10.1016/j.neuropharm.2021.108719

DO - 10.1016/j.neuropharm.2021.108719

M3 - Review

C2 - 34273389

AN - SCOPUS:85113725815

VL - 196

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

M1 - 108719

ER -

ID: 285939647