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Biochem Biophys Res Commun. 2017 Feb 19;483(4):1143-1147. doi: 10.1016/j.bbrc.2016.09.062. Epub 2016 Sep 14.

Cellular prion protein as a receptor for amyloid-β oligomers in Alzheimer's disease.

Author information

1
Cellular Neuroscience, Neurodegeneration & Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
2
Cellular Neuroscience, Neurodegeneration & Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT, USA. Electronic address: Stephen.Strittmatter@yale.edu.

Abstract

Soluble oligomers of amyloid-beta (Aβo) are implicated by biochemical and genetic evidence as a trigger for Alzheimer's disease (AD) pathophysiology. A key step is Aβo interaction with the neuronal surface to initiate a cascade of altered signal transduction leading to synaptic dysfunction and damage. This review discusses neuronal cell surface molecules with high affinity selectively for oligomeric disease-associated states of Aβ, with a particular focus on the role of cellular prion protein (PrPC) in this process. Additional receptors may contribute to mediation of Aβo action, but PrPC appears to play a primary role in a number of systems. The specificity of binding, the genetic necessity in mouse models of disease and downstream signaling pathways are considered. Signal transduction downstream of Aβo complexes with PrPC involves metabotropic glutamate receptor 5 (mGluR5), Fyn kinase and Pyk2 kinase, with deleterious effects on synaptic transmission and maintenance. Current data support the hypothesis that a substantial portion of Aβo toxicity in AD is mediated after initial interaction with PrPC on the neuronal surface. As such, the interaction of Aβo with PrPC is a potential therapeutic intervention site for AD.

KEYWORDS:

Alzheimer's disease; Cellular prion protein

PMID:
27639648
PMCID:
PMC5303667
DOI:
10.1016/j.bbrc.2016.09.062
[Indexed for MEDLINE]
Free PMC Article

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