Editing NMDA receptor (section)

===Excitotoxicity in a clinical setting===
Excitotoxicity has been thought to play a role in the degenerative properties of [[Neurodegeneration|neurodegenerative]] conditions since the late 1950s.<ref>{{cite journal | vauthors = Lucas DR, Newhouse JP | title = The toxic effect of sodium L-glutamate on the inner layers of the retina | journal = A.M.A. Archives of Ophthalmology | volume = 58 | issue = 2 | pages = 193–201 | date = August 1957 | pmid = 13443577 | doi = 10.1001/archopht.1957.00940010205006 }}</ref> NMDA receptors seem to play an important role in many of these degenerative diseases affecting the brain. Most notably, excitotoxic events involving NMDA receptors have been linked to Alzheimer's disease and Huntington's disease, as well as with other medical conditions such as strokes and epilepsy.<ref name=":0" /><ref name="pmid20152125">{{cite journal | vauthors = Milnerwood AJ, Gladding CM, Pouladi MA, Kaufman AM, Hines RM, Boyd JD, Ko RW, Vasuta OC, Graham RK, Hayden MR, Murphy TH, Raymond LA | display-authors = 6 | title = Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice | journal = Neuron | volume = 65 | issue = 2 | pages = 178–190 | date = January 2010 | pmid = 20152125 | doi = 10.1016/j.neuron.2010.01.008 | s2cid = 12987037 | doi-access = free }}</ref> Treating these conditions with one of the many known NMDA receptor antagonists, however, leads to a variety of unwanted side effects, some of which can be severe. These side effects are, in part, observed because the NMDA receptors do not just signal for cell death but also play an important role in its vitality.<ref name=":2" /> Treatment for these conditions might be found in blocking NMDA receptors not found at the synapse.<ref name=":0" /><ref name=":4"/> One class of excitotoxicity in disease includes gain-of-function mutations in GRIN2B and GRIN1 associated with cortical malformations, such as [[polymicrogyria]].<ref>{{cite journal | vauthors = Smith RS, Walsh CA | title = Ion Channel Functions in Early Brain Development | journal = Trends in Neurosciences | volume = 43 | issue = 2 | pages = 103–114 | date = February 2020 | pmid = 31959360 | pmc = 7092371 | doi = 10.1016/j.tins.2019.12.004 }}</ref> D-serine, an antagonist/inverse co-agonist of ''t''-NMDA receptors, which is made in the brain, has been shown to mitigate neuron loss in an animal model of [[temporal lobe epilepsy]].<ref name=":3" />