Endothelial LRP1 - A Potential Target for the Treatment of Alzheimer's Disease : Theme: Drug Discovery, Development and Delivery in Alzheimer's Disease Guest Editor: Davide Brambilla

Pharm Res. 2017 Dec;34(12):2637-2651. doi: 10.1007/s11095-017-2267-3. Epub 2017 Sep 25.

Abstract

The accumulation of the neurotoxin beta-amyloid (Aβ) is a major hallmark in Alzheimer's disease (AD). Aβ homeostasis in the brain is governed by its production and various clearance mechanisms. Both pathways are influenced by the ubiquitously expressed low-density lipoprotein receptor-related protein 1 (LRP1). In cerebral blood vessels, LRP1 is an important mediator for the rapid removal of Aβ from brain via transport across the blood-brain barrier (BBB). Here, we summarize recent findings on LRP1 function and discuss the targeting of LRP1 as a modulator for AD pathology and drug delivery into the brain.

Keywords: Alzheimer's disease; LRP1; angiopeps; beta-amyloid; blood-brain barrier; choroid plexus; drug delivery; targeting.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Drug Delivery Systems* / methods
  • Drug Discovery* / methods
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Molecular Targeted Therapy / methods

Substances

  • Amyloid beta-Peptides
  • LRP1 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-1