Amyloid-β Receptors: The Good, the Bad, and the Prion Protein

Heledd H Jarosz-Griffiths; Elizabeth Noble; Jo V Rushworth; Nigel M Hooper

doi:10.1074/jbc.R115.702704

Amyloid-β Receptors: The Good, the Bad, and the Prion Protein

J Biol Chem. 2016 Feb 12;291(7):3174-83. doi: 10.1074/jbc.R115.702704. Epub 2015 Dec 30.

Authors

Heledd H Jarosz-Griffiths¹, Elizabeth Noble¹, Jo V Rushworth², Nigel M Hooper³

Affiliations

¹ From the Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT and.
² the Faculty of Health and Life Sciences, De Montfort University, Leicester LE1 9BH, United Kingdom.
³ From the Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT and nigel.hooper@manchester.ac.uk.

Abstract

Several different receptor proteins have been identified that bind monomeric, oligomeric, or fibrillar forms of amyloid-β (Aβ). "Good" receptors internalize Aβ or promote its transcytosis out of the brain, whereas "bad" receptors bind oligomeric forms of Aβ that are largely responsible for the synapticloss, memory impairments, and neurotoxicity that underlie Alzheimer disease. The prion protein both removes Aβ from the brain and transduces the toxic actions of Aβ. The clustering of distinct receptors in cell surface signaling platforms likely underlies the actions of distinct oligomeric species of Aβ. These Aβ receptor-signaling platforms provide opportunities for therapeutic intervention in Alzheimer disease.

Keywords: Alzheimer disease; amyloid; oligomer; prion; receptor.

Publication types

Comparative Study
Review

MeSH terms

Alzheimer Disease / drug therapy
Alzheimer Disease / metabolism*
Alzheimer Disease / pathology
Alzheimer Disease / prevention & control
Amyloid beta-Peptides / antagonists & inhibitors
Amyloid beta-Peptides / chemistry
Amyloid beta-Peptides / metabolism*
Animals
Apoptosis / drug effects
Humans
Ligands
Low Density Lipoprotein Receptor-Related Protein-1 / agonists
Low Density Lipoprotein Receptor-Related Protein-1 / metabolism
Models, Biological*
Molecular Targeted Therapy
Nerve Tissue Proteins / antagonists & inhibitors
Nerve Tissue Proteins / chemistry
Nerve Tissue Proteins / metabolism*
Neurons / drug effects
Neurons / metabolism*
Neurons / pathology
Nootropic Agents / pharmacology
Nootropic Agents / therapeutic use
PrPC Proteins / agonists
PrPC Proteins / antagonists & inhibitors
PrPC Proteins / metabolism
Protein Aggregates / drug effects
Protein Aggregation, Pathological / drug therapy
Protein Aggregation, Pathological / metabolism
Protein Aggregation, Pathological / pathology
Protein Aggregation, Pathological / prevention & control
Protein Isoforms / antagonists & inhibitors
Protein Isoforms / chemistry
Protein Isoforms / metabolism
Receptor Aggregation / drug effects
Receptor for Advanced Glycation End Products / agonists
Receptor for Advanced Glycation End Products / metabolism
Receptors, Cell Surface / agonists*
Receptors, Cell Surface / antagonists & inhibitors
Receptors, Cell Surface / metabolism
Receptors, N-Methyl-D-Aspartate / agonists
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate / metabolism
Signal Transduction* / drug effects
Transcytosis / drug effects

Substances

Amyloid beta-Peptides
Ligands
Low Density Lipoprotein Receptor-Related Protein-1
Nerve Tissue Proteins
Nootropic Agents
PrPC Proteins
Protein Aggregates
Protein Isoforms
Receptor for Advanced Glycation End Products
Receptors, Cell Surface
Receptors, N-Methyl-D-Aspartate

Abstract

Publication types

MeSH terms

Substances

Grants and funding