Species: Hu
Applications: Binding Activity
Species: Hu
Applications: Bioactivity
Description
Apolipoprotein E (ApoE) is a polymorphic lipid-transport
protein with three major human isoforms—ApoE2, ApoE3, and ApoE4—differing by
single amino acid substitutions at residues 112 and 158, which significantly
alter their structure and function [1, 2].
All isoforms share a two-domain structure: the N-terminal domain
mediates receptor binding, while the C-terminal domain facilitates lipid
binding and oligomerization [2]. ApoE3 (Cys112/Arg158) is the most common and
functionally neutral isoform, while ApoE2 (Cys112/Cys158) has reduced affinity
for LDL receptors, often leading to type III hyperlipoproteinemia in
homozygotes [1, 4]. ApoE4 (Arg112/Arg158) exhibits a more compact and less
stable structure due to domain interaction, predisposing it to pathological
effects in the brain [2, 5]. Functionally, ApoE isoforms differentially
regulate neuronal metabolism: ApoE2 enhances glycolytic activity and hexokinase
expression, promoting neuroprotection, whereas ApoE4 impairs these pathways,
increasing vulnerability to aging and Alzheimer's disease (AD) [1]. Recent
transcriptomic and epigenomic profiling of human microglia in an AD
xenotransplantation model revealed that ApoE isoforms distinctly shape gene
expression and chromatin accessibility. ApoE4 drives pro-inflammatory and
neurodegenerative signatures, while ApoE2 supports homeostatic microglial
states [3]. Clinically, ApoE genotyping is widely used to assess AD risk, with
ApoE4 being the strongest genetic risk factor and ApoE2 offering relative
protection [4, 5]. Therapeutic strategies targeting ApoE include
isoform-specific modulation and gene editing. Additionally, ApoE isoforms are
valuable tools in translational research for drug screening, biomarker
discovery, and personalized medicine [4].
Bioinformatics
| Uniprot |
|
| Product By Gene ID |
348 |
| Alternate Names |
- AD2
- Apo-E
- ApoE4
- apolipoprotein E
- Apolipoprotein E3
- LDLCQ5
- LPG
|