CIDeRplusGeneral Information:
| Id: | 6,894 (click here to show other Interactions for entry) |
| Diseases: |
Diabetes mellitus, type II
- [OMIM]
Insulin resistance |
| Mammalia | |
| review | |
| Reference: | Salameh TS et al.(2016) Insulin resistance, dyslipidemia, and apolipoprotein E interactions as mechanisms in cognitive impairment and Alzheimers disease Exp. Biol. Med. (Maywood) 241: 1676-1683 [PMID: 27470930] |
Interaction Information:
| Comment | In humans, there are three alleles of APOE: E2, E3, and E4. The APOE4 protein is folded into a more compact structure compared to the other APOE isoforms, leading to a decreased ability to bind lipids and a higher likelihood of cleavage into neurotoxic fragments. Perivascular removal of amyloid beta (Abeta) is hindered with the expression of E4, which was shown in many in vitro studies as well as in mice expressing human E4. This decreased drainage, in turn, leads to decreased clearance of Abeta peptides and increased amyloid plaques, as well as other pathophysiologic features such as alterations in the neurovascular unit and blood‚Äďbrain barrier (BBB) function. |
|
Formal Description Interaction-ID: 67343 |
|
| Comment | In humans, there are three alleles of APOE: E2, E3, and E4. The APOE4 protein is folded into a more compact structure compared to the other APOE isoforms, leading to a decreased ability to bind lipids and a higher likelihood of cleavage into neurotoxic fragments. Perivascular removal of amyloid beta (Abeta) is hindered with the expression of E4, which was shown in many in vitro studies as well as in mice expressing human E4. This decreased drainage, in turn, leads to decreased clearance of Abeta peptides and increased amyloid plaques, as well as other pathophysiologic features such as alterations in the neurovascular unit and blood‚Äďbrain barrier (BBB) function. |
|
Formal Description Interaction-ID: 67344 |
gene/protein mutant decreases_activity of |
| Comment | In humans, there are three alleles of APOE: E2, E3, and E4. The APOE4 protein is folded into a more compact structure compared to the other APOE isoforms, leading to a decreased ability to bind lipids and a higher likelihood of cleavage into neurotoxic fragments. Perivascular removal of amyloid beta (Abeta) is hindered with the expression of E4, which was shown in many in vitro studies as well as in mice expressing human E4. This decreased drainage, in turn, leads to decreased clearance of Abeta peptides and increased amyloid plaques, as well as other pathophysiologic features such as alterations in the neurovascular unit and blood‚Äďbrain barrier (BBB) function. |
|
Formal Description Interaction-ID: 67345 |
|
| Comment | APOE4 knock-in mice had higher levels of blood‚Äďbrain barrier (BBB) breakdown in response to injury, via upregulation of the proinflammatory cyclophilin A pathway in pericytes. |
|
Formal Description Interaction-ID: 67346 |
|
| Drugbank entries | Show/Hide entries for PPIA |
| Comment | The role that APOE plays in transport and clearance of molecules depends on the APOE isoform, and these transport differences may be related to differences in receptor utilization for the isoforms, with APOE4-Abeta complexes using the very low-density lipoprotein (VLDL) receptor and the other isoforms using LRP-1. These isoform specific differences may also affect how the blood-brain barrier (BBB) transports insulin, free fatty acids (FFAs), and other metabolites involved in cognitive processes. |
|
Formal Description Interaction-ID: 67347 |
|
| Comment | APOE4 carrier status is correlated with increased LDL and triglyceride levels, and an increased risk of heart disease. |
|
Formal Description Interaction-ID: 67350 |
gene/protein mutant increases_activity of |
| Comment | APOE4 carrier status is correlated with increased LDL and triglyceride levels, and an increased risk of heart disease. |
|
Formal Description Interaction-ID: 67351 |
gene/protein mutant increases_activity of phenotype |
| Comment | APOE4 carrier status is correlated with increased LDL and triglyceride levels, and an increased risk of heart disease. |
|
Formal Description Interaction-ID: 67352 |
|
| Comment | APOE4 carriers showed poorer responses to intranasal insulin treatment compared to patients who were E4 noncarriers. |
|
Formal Description Interaction-ID: 67358 |
|
| Comment | APOE4 positive individuals have more exaggerated plasma lipid changes after high-fat diet intake. |
|
Formal Description Interaction-ID: 67365 |
|