| LRP8 (ApoER2) | |
|---|---|
| Gene | [LRP8](/genes/lrp8) |
| UniProt | Q9Y6X0 |
| PDB | 1JYH, 1OXM |
| Mol. Weight | ~110 kDa |
| Localization | Plasma membrane, Postsynaptic density, Synapses |
| Family | LDL receptor family (LDLR) |
| Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Atherosclerosis](/diseases/atherosclerosis) |
LRP8 (also known as ApoER2 or apolipoprotein E receptor 2) is a member of the LDL receptor family that plays crucial roles in synaptic function, Reelin signaling, and neuronal migration. It is particularly important in the central nervous system where it mediates signaling events critical for learning, memory, and neuronal plasticity. LRP8 has been implicated in the pathogenesis of Alzheimer's disease and other neurodegenerative disorders[1].
LRP8 (ApoER2) is a transmembrane receptor protein belonging to the LDL receptor superfamily. It is highly expressed in the brain, particularly in the hippocampus, cortex, and cerebellum. LRP8 functions as a receptor for apolipoprotein E (ApoE) isoforms and Reelin, playing essential roles in synaptic plasticity, dendritic spine formation, and neuronal migration during development[2].
LRP8 is a type I transmembrane protein with the following structural features:
LRP8 is a critical receptor for the extracellular matrix protein Reelin:
LRP8 plays essential roles in synaptic plasticity:
As an ApoE receptor, LRP8 participates in:
LRP8 interacts differentially with ApoE isoforms:
LRP8 is implicated in AD pathogenesis through multiple mechanisms:
In PD, LRP8 may contribute to:
LRP8 represents a potential therapeutic target:
Herz J, Chen Y. Reelin, lipoprotein receptors and synaptic plasticity. 2006. ↩︎
D'Arcangelo G, Miao GG, Chen SC, et al. A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. 1995. ↩︎
Hiesberger T, Trommsdorff M, Howell BW, et al. Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation. 1999. ↩︎
Hoe HS, Lee KJ, Carney RS, et al. Engagement of alpha7 nicotinic acetylcholine receptor by endogenous acetylcholine prevents beta-amyloid peptide neurotoxicity. 2009. ↩︎
Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. 2012. ↩︎
Lane-Donovan C, Philips GT, Herz J. More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration. 2014. ↩︎