Low-Density Lipoprotein Receptor-Related Protein 8 at the Crossroad between Cancer and Neurodegeneration

Related Experiment Video

Updated: Aug 30, 2025

Monitoring Leucine-Rich Repeat Containing 8 Channel (LRRC8/VRAC) Activity Using Sensitized-Emission Förster Resonance Energy Transfer (SE-FRET)
08:54

Monitoring Leucine-Rich Repeat Containing 8 Channel (LRRC8/VRAC) Activity Using Sensitized-Emission Förster Resonance Energy Transfer (SE-FRET)

Published on: August 9, 2024

503

Daniela Passarella1, Silvia Ciampi1, Valentina Di Liberto2

  • 1Department of Medicine and Health Sciences "V. Tiberio", University of Molise, 86100 Campobasso, Italy.

International Journal of Molecular Sciences
|August 26, 2022
PubMed

Insights

Low-density lipoprotein receptor-related protein 8 (LRP8) plays a dual role in cell proliferation and neurodegeneration. Its function depends on specific interactions and processing, impacting cancer and Alzheimer

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Neuroscience
  • Oncology

Background:

  • Low-density lipoprotein receptors (LDLRs) are cell surface proteins crucial for lipid homeostasis, cell migration, proliferation, and differentiation.
  • The LDLR family exhibits structural similarities but significant functional differences due to tissue-specific interactions and proteolytic processing.
  • Low-density lipoprotein receptor-related protein 8 (LRP8) is increasingly recognized for its involvement in both cancer and neurodegenerative diseases.

Purpose of the Study:

  • To review the multifaceted roles of LDLRs, with a specific focus on LRP8, in the context of cancer and neurodegeneration.
  • To elucidate how LRP8's interactions and processing influence its contribution to proliferative and neurodegenerative processes.

Main Methods:

  • Literature review of recent studies on LDLR family members, particularly LRP8.
  • Analysis of LRP8's involvement in cancer pathways through overexpression data.
  • Examination of LRP8's role in neurodegeneration via its interactions with apolipoprotein E (ApoE), reelin, and its function as a γ-secretase substrate.

Main Results:

  • LRP8 overexpression is observed in various cancers, including breast, gastric, prostate, lung, and melanoma, suggesting a role in cancer progression.
  • LRP8 acts as a receptor for apolipoprotein E (ApoE), a major risk factor for Alzheimer's disease (AD).
  • LRP8 is implicated in neuronal migration (via reelin) and is a substrate for γ-secretase, an enzyme central to amyloid formation in AD.

Conclusions:

  • LRP8 exhibits pleiotropic functions, acting as a critical mediator in both cancer development and neurodegenerative processes like AD.
  • The specific biological outcome (proliferative or neurodegenerative) is contingent upon LRP8's unique interactions and proteolytic processing.
  • Understanding LRP8's dual role offers potential therapeutic targets for both cancer and Alzheimer's disease.
Keywords:
Alzheimer’s diseaseLDL receptor familyLRP8apolipoproteincancer

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