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Table 1 Selected studies on APOE and endoplasmic reticulum stress

From: APOE genotype and stress response - a mini review

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 ↑

  1. ATF4 activating transcription factor 4, ATF6 activating transcription factor 6, ATG7 autophagy related 7, APOE apolipoprotein E, BIP binding immunoglobulin protein, CHOP c/EBP-homologous protein 10, EGFP enhanced green fluorescent protein, ER endoplasmic reticulum, FOXN3 forkhead box N3, GADD34 protein phosphatase 1, regulatory subunit 15A, GCN eukaryotic translation initiation factor 2 alpha kinase 4, GRP94 heat shock protein 90, beta, HERP homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1, IRE1α serine/threonine-protein kinase/endoribonuclease, JNK mitogen-activated protein kinase 8, OASIS old astrocyte specifically induced substance, PDI protein disulfide isomerase associated 3, PERK eukaryotic translation initiation factor 2-alpha kinase 3, PKR eukaryotic translation initiation factor 2-alpha kinase 2, TRB3 tribbles homolog 3, UBA5 ubiquitin like modifier activating enzyme 5, XBP1 X-box binding protein 1