The DOI matches its Crossref record; 246 of the 246 references it cites were found in a registry or an index.
Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration
Open accessAbstract
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.
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Cites
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Cited by
The mechanisms of ferroptosis and its role in alzheimer’s disease
Ma, H., Dong, Y., Chu, Y., Guo, Y., & Li, L. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.965064 · Cited by 115
Andersen, J. V., Skotte, N. H., Christensen, S. K., Polli, F. S., Shabani, M., Markussen, K. H., Haukedal, H., Westi, E. W., Diaz-delCastillo, M., Sun, R. C., et al. (2021) · Cell Death & Disease · doi:10.1038/s41419-021-04237-y · Cited by 104
Self-citationMetabolic regulation of microglial phagocytosis: Implications for Alzheimer's disease therapeutics
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Andersen, J. V., Marian, O. C., Qvist, F. L., Westi, E. W., Aldana, B. I., Schousboe, A., Don, A. S., Skotte, N. H., & Wellendorph, P. (2024) · Glia · doi:10.1002/glia.24585 · Cited by 13
Self-citationWalecha, V., & Luthra, P. M. (2025) · Neurochemical Research · doi:10.1007/s11064-025-04559-9 · Cited by 12
Metadata
- Authors
- Andersen, J. V., Markussen, K. H., Jakobsen, E., Schousboe, A., Waagepetersen, H. S., Rosenberg, P. A., & Aldana, B. I.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 196
- Pages
- 108719
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W3179730861
- Cited by
- 371
- References
- 246
- FWCI
- 22.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- 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. https://doi.org/10.1016/j.neuropharm.2021.108719
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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