若干代表性基因检测位点的功能介绍.pptVIP

Lipid-associated apolipoprotein E (APOE) could impede reelin-induced signalling by competing for lipoprotein receptor binding3, 88 (a). Impaired reelin signalling results in elevated phosphorylation4, which could in turn lead to the formation of neurofibrillary tangles (NFTs) (b). APOE might also inhibit reelin-mediated potentiation of NMDA (N-methyl-D-aspartate) receptor (NMDAR) activity and synaptic plasticity (c). After binding to low-density lipoprotein receptor (LDLR)-related proteins (LRP), APOE-containing lipoproteins undergo endocytosis (d). Different APOE isoforms might differentially affect intracellular trafficking131, 132 of the NMDAR (through association with APOE receptors84, 87) and thereby affect its functional availability. Cholesterol homeostasis has a profound impact on the production and trafficking of the amyloid- (A) peptide6, 51, 133 (e). Extracellular A could associate with APOE and get cleared through receptor-mediated endocytosis (f). Extracellular A represses NMDAR activity52 directly, but also by promoting the endocytosis of NMDARs120 (g). Reduced glutamatergic transmission could result in impaired synaptic plasticity and promote neuronal loss and dementia. APOER2, APOE receptor 2; DAB1, disabled 1; GSK3b;, gylcogen synthase kinase 3; PKB, protein kinase B; SFKs, SRC family tyrosine kinases; VLDLR, very-low-density lipoprotein receptor. * In order to make and store a memory, the NMDA receptor on a nerve cell must be triggered to cause the cell to fire for a sufficiently long time, producing a long-lasting synaptic response that ultimately results in the storing of a new memory. The APOE protein that binds to the APOE receptor is believed to transport cellular debris as the result of normal metabolism or injury away from cells in the brain, moving debris to areas where it can be completely removed from the brain.? There are eight different APOE receptor types.? APOE receptor 2 type (ApoEr2 ), is believed to be critical to the development