Editing Notch signaling pathway (section)

=== Adult brain function ===

Apart from its role in development, evidence shows that Notch signaling is also involved in neuronal apoptosis, neurite retraction, and neurodegeneration of ischemic stroke in the brain<ref>{{cite journal | vauthors = Woo HN, Park JS, Gwon AR, Arumugam TV, Jo DG | title = Alzheimer's disease and Notch signaling | journal = Biochemical and Biophysical Research Communications | volume = 390 | issue = 4 | pages = 1093–1097 | date = December 2009 | pmid = 19853579 | doi = 10.1016/j.bbrc.2009.10.093 }}</ref> In addition to developmental functions, Notch proteins and ligands are expressed in cells of the adult nervous system,<ref>{{cite journal | vauthors = Presente A, Andres A, Nye JS | title = Requirement of Notch in adulthood for neurological function and longevity | journal = NeuroReport | volume = 12 | issue = 15 | pages = 3321–3325 | date = October 2001 | pmid = 11711879 | doi = 10.1097/00001756-200110290-00035 | s2cid = 8329715 }}</ref> suggesting a role in CNS plasticity throughout life. Adult mice heterozygous for mutations in either Notch1 or Cbf1 have deficits in spatial learning and memory.<ref name="learning" /> Similar results are seen in experiments with [[presenilin]]s1 and 2, which mediate the Notch intramembranous cleavage. To be specific, conditional deletion of presenilins at 3 weeks after birth in excitatory neurons causes learning and memory deficits, neuronal dysfunction, and gradual neurodegeneration.<ref name="pmid15066262">{{cite journal | vauthors = Saura CA, Choi SY, Beglopoulos V, Malkani S, Zhang D, Shankaranarayana Rao BS, Chattarji S, Kelleher RJ, Kandel ER, Duff K, Kirkwood A, Shen J | display-authors = 6 | title = Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration | journal = Neuron | volume = 42 | issue = 1 | pages = 23–36 | date = April 2004 | pmid = 15066262 | doi = 10.1016/S0896-6273(04)00182-5 | s2cid = 17550860 | doi-access = free }}</ref> Several [[gamma secretase]] inhibitors that underwent human clinical trials in [[Alzheimer's disease]] and [[Mild cognitive impairment|MCI]] patients resulted in statistically significant worsening of cognition relative to controls, which is thought to be due to its incidental effect on Notch signalling.<ref>{{cite journal | vauthors = De Strooper B | title = Lessons from a failed γ-secretase Alzheimer trial | journal = Cell | volume = 159 | issue = 4 | pages = 721–726 | date = November 2014 | pmid = 25417150 | doi = 10.1016/j.cell.2014.10.016 | doi-access = free }}</ref>