General 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–brain barrier (BBB) function.
Formal Description
Interaction-ID: 67343

gene/protein mutant

APOE (isoform E4)

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–brain barrier (BBB) function.
Formal Description
Interaction-ID: 67344

gene/protein mutant

APOE (isoform E4)

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–brain barrier (BBB) function.
Formal Description
Interaction-ID: 67345

gene/protein mutant

APOE (isoform E4)

increases_activity of

Comment APOE4 knock-in mice had higher levels of blood–brain barrier (BBB) breakdown in response to injury, via upregulation of the proinflammatory cyclophilin A pathway in pericytes.
Formal Description
Interaction-ID: 67346

gene/protein mutant

APOE (isoform E4)

increases_activity of

gene/protein

PPIA

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

gene/protein mutant

APOE (isoform E4)

interacts (colocalizes) with

gene/protein

VLDLR

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

APOE (isoform E4)

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

APOE (isoform E4)

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: 67352

gene/protein mutant

APOE (isoform E4)

increases_activity of

disease

Cardiovascular disease

Comment APOE4 carriers showed poorer responses to intranasal insulin treatment compared to patients who were E4 noncarriers.
Formal Description
Interaction-ID: 67358

gene/protein mutant

APOE (isoform E4)

affects_activity of

environment

intranasal insulin

Comment APOE4 positive individuals have more exaggerated plasma lipid changes after high-fat diet intake.
Formal Description
Interaction-ID: 67365

gene/protein mutant

APOE (isoform E4)

affects_activity of