Reference | Model system | ER stress-relevant findings in E4-carrying cells |
---|---|---|
Sabaretnam et al. [80] | APOE4 vs. APOE3 transfected HepG2 cells | - Trafficking velocity ↓ |
Zhong et al. [75] | Primary astrocytes from Arg-61 APOE mice vs. wild type mice astrocytes | - Intracellular APOE concentration↓ - Levels and fragmentation of Oasis ↑ - Levels of UPR components and downstream effectors (ATF4, XBP1, BIP, GRP94, PDI, GADD34, Herp, CHOP) ↑ |
Brodbeck et al. [76] | EGFP-APOE4 vs. EGFP-APOE3 transfected Neuro-2a cells and primary murine hippocampal neurons | - Retention of APOE in Golgi and ER ↑ - Trafficking of APOE in the Golgi/Soma ↓ - PERK, ATF6, XBP1, IRE1ɑ, CHOP, BIP protein levels ↔ Impaired EGFP-APOE4 trafficking rescued by R61T mutation or APOE4 structure correctors. |
Eberlé et al. [78] | Primary peritoneal macrophages from Arg-61 APOE vs. Thr-61 APOE mice | - APOE secretion ↓ - ATF4, CHOP, TRB3 mRNA levels ↔ |
Cash et al. [79] | Primary peritoneal macrophages from APOE4 vs. APOE3 TR mice | - Inflammation-induced apoptosis ↑ - Efferocytosis ↓ - Basal and stimulated conditions: JNK phosphorylation ↑ - Stimulated conditions: IRE1ɑ, PERK phosphorylation ↑ XBP1(S), CHOP mRNA and protein levels ↑ Improved efferocytosis, reduced apoptosis after tauroursodeoxycholic acid treatment. |
Simpson et al. [81] | Human astrocyte transcriptome (lateral temporal cortex; APOE ε4 carriers vs. non-carriers) | Altered pathways incl. transcription (ATF4, FOXN3) and ubiquitin-mediated proteolysis (ATG7, UBA5) |
Segev et al. [77] | APOE4 vs. APOE3 TR mice (age: 4 months, cortex and hippocampus) | - Phosphorylation of eIF2ɑ, GCN2, PKR ↑ |