The DOI matches its Crossref record; 92 of the 92 references it cites were found in a registry or an index.
Glutamate, Glutamate Receptors, and Downstream Signaling Pathways
Open accessAbstract
Glutamate is a nonessential amino acid, a major bioenergetic substrate for proliferating normal and neoplastic cells, and an excitatory neurotransmitter that is actively involved in biosynthetic, bioenergetic, metabolic, and oncogenic signaling pathways. Glutamate signaling activates a family of receptors consisting of metabotropic glutamate receptors (mGluRs) and ionotropic glutamate receptors (iGluRs), both of which have been implicated in chronic disabling brain disorders such as Schizophrenia and neurodegenerative diseases like Alzheimer's, Parkinson's, and multiple sclerosis. In this review, we discuss the structural and functional relationship of mGluRs and iGluRs and their downstream signaling pathways. The three groups of mGluRs, the associated second messenger systems, and subsequent activation of PI3K/Akt, MAPK, NFkB, PLC, and Ca/CaM signaling systems will be discussed in detail. The current state of human mGluR1a as one of the most important isoforms of Group I-mGluRs will be highlighted. The lack of studies on the human orthologues of mGluRs family will be outlined. We conclude that upon further study, human glutamate-initiated signaling pathways may provide novel therapeutic opportunities for a variety of non-malignant and malignant human diseases.
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Cites
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Pajarillo, E., Rizor, A., Lee, J., Aschner, M., & Lee, E. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.03.002 · Cited by 478
Singewald, N., Schmuckermair, C., Whittle, N., Holmes, A., & Ressler, K. J. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.12.004 · Cited by 390
“Group II (mGluR2, mGluR3) and Group III (mGluR4, mGluR6–mGluR8) are both coupled to Gi proteins inhibiting adenylate cyclase (AC) activity and expressed on pre- as well as postsynaptic sites (Willard & Koochekpour, 2013).”
BackgroundThe glutamate hypothesis of schizophrenia: evidence from human brain tissue studies
Hu, W., MacDonald, M. L., Elswick, D. E., & Sweet, R. A. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12547 · Cited by 286
Green, J. L., dos Santos, W. F., & Fontana, A. C. K. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114786 · Cited by 150
Metadata
- Authors
- Willard, S. S., & Koochekpour, S.
- Venue
- International Journal of Biological Sciences
- Publisher
- Ivyspring International Publisher
- Published
- 2013
- Volume
- 9
- Issue
- 9
- Pages
- 948-959
- ISSN
- 1449-2288 (ISSN-L)
- OpenAlex
- W2154168677
- Cited by
- 323
- References
- 92
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- gold
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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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