Glud2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
{{Infobox gene
| symbol = GLUD2
| name = Glutamate Dehydrogenase 2
| chromosome = 12
| locus = 12q24.13
| geneID = 2717
| omim = 300144
| ensembl = ENSG00000166503
| uniprot = P49448
| uniprot_name = GLUD2
| diseases = Alzheimer's Disease, Parkinson's Disease, Huntington's Disease
| diseases_ref = Plaitakis et al., 2017, J Neurochem
}}
Glutamate dehydrogenase 2 (GLUD2) is a mitochondrial enzyme that catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate, linking amino acid metabolism to the TCA cycle. The GLUD2 gene is located on chromosome 6q24.2 and encodes a protein of 505 amino acids. GLUD2 is a vertebrate-specific, neuronally expressed isoform derived from a retrotransposed copy of GLUD1. Unlike GLUD1, GLUD2 is allosterically activated by GTP and ADP and inhibited by ATP, making it sensitive to cellular energy status. In the brain, GLUD2 supports neurotransmitter glutamate recycling (glutamate-glutamine cycle), ammonia detoxification, and energy metabolism. GLUD2 is implicated in Alzheimer's disease, Parkinson's disease, and Huntington's disease.
Glutamate dehydrogenase 2 (GLUD2) is a mitochondrial enzyme that catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate. GLUD2 is the brain-specific isoform, distinct from the ubiquitous GLUD1, and plays a crucial role in glutamate and GABA metabolism.
GLUD2 catalyzes: Glutamate + NAD(P)+ + H2O → α-Ketoglutarate + NAD(P)H + NH4+ + H+
This reaction links:
GLUD2 is crucial for brain ammonia handling:
In synaptic terminals, GLUD2:
GLUD2 is altered in AD:
GLUD2 dysfunction in PD:
GLUD2 in HD:
GLUD2 is brain-specific:
Cellular localization:
The study of Glud2 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Plaitakis A et al.. "Evolution of Glutamate Metabolism via ." International journal of molecular sciences (2024) DOI:10.3390/ijms25105297
Shashidharan P, Plaitakis A. "The discovery of human of GLUD2 glutamate dehydrogenase and its implications for cell function in health and disease." Neurochemical research (2014) DOI:10.1007/s11064-013-1227-5
Nakamoto C et al.. "Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain." The Journal of comparative neurology (2020) DOI:10.1002/cne.24792
Plaitakis A, Latsoudis H, Spanaki C. "The human GLUD2 glutamate dehydrogenase and its regulation in health and disease." Neurochemistry international (2011) DOI:10.1016/j.neuint.2011.03.015
Yuzaki M. "The ins and outs of GluD2--why and how Purkinje cells use the special glutamate receptor." Cerebellum (London, England) (2012) DOI:10.1007/s12311-011-0328-4
Lemoine D et al.. "Probing the ionotropic activity of glutamate GluD2 receptor in HEK cells with genetically-engineered photopharmacology." eLife (2020) DOI:10.7554/eLife.59026
Ady V et al.. "Type 1 metabotropic glutamate receptors (mGlu1) trigger the gating of GluD2 delta glutamate receptors." EMBO reports (2014) DOI:10.1002/embr.201337371
Spanaki C et al.. "Glutamate-specific gene linked to human brain evolution enhances synaptic plasticity and cognitive processes." iScience (2024) DOI:10.1016/j.isci.2024.108821