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Cellular prion protein as a therapeutic target in Alzheimer's disease.
J Alzheimers Dis. 2014; 38(2):227-44.JA

Abstract

Soluble oligomeric species of amyloid-β (Aβ) peptide are presumed to be drivers of synaptic impairment, and the resulting cognitive dysfunction in Alzheimer's disease. In 2009, cellular prion protein (PrPC) was identified in a genome-wide screen as a high-affinity receptor for Aβ oligomers, and since then, many studies have explored the role of PrPC in Alzheimer's disease. Herein, I systematically assess the current level of target validation for PrPC in Alzheimer's disease and the merits of the identified approaches to therapeutically affect the PrPC:Aβ oligomer-interaction. The interaction of Aβ oligomers with PrPC in mice impairs hippocampal long-term potentiation, memory, and learning in a manner that involves Fyn, tau, and glutamate receptors. Furthermore, PrPC acts to catalyze the formation of certain Aβ oligomeric species in the synapse and may mediate the toxic effects of other β-sheet rich oligomers as well. Therapeutic approaches utilizing soluble PrPC ectodomain or monoclonal antibodies targeting PrPC can at least partially prevent the neurotoxic effects of Aβ oligomers in mice.

Authors+Show Affiliations

Massachusetts Institute of Technology, Cambridge, MA, USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23948943

Citation

Laurén, Juha. "Cellular Prion Protein as a Therapeutic Target in Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 38, no. 2, 2014, pp. 227-44.
Laurén J. Cellular prion protein as a therapeutic target in Alzheimer's disease. J Alzheimers Dis. 2014;38(2):227-44.
Laurén, J. (2014). Cellular prion protein as a therapeutic target in Alzheimer's disease. Journal of Alzheimer's Disease : JAD, 38(2), 227-44. https://doi.org/10.3233/JAD-130950
Laurén J. Cellular Prion Protein as a Therapeutic Target in Alzheimer's Disease. J Alzheimers Dis. 2014;38(2):227-44. PubMed PMID: 23948943.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cellular prion protein as a therapeutic target in Alzheimer's disease. A1 - Laurén,Juha, PY - 2013/8/17/entrez PY - 2013/8/21/pubmed PY - 2014/6/28/medline KW - Alzheimer's disease KW - amyloid-β peptides KW - c-fyn protein KW - prion protein SP - 227 EP - 44 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 38 IS - 2 N2 - Soluble oligomeric species of amyloid-β (Aβ) peptide are presumed to be drivers of synaptic impairment, and the resulting cognitive dysfunction in Alzheimer's disease. In 2009, cellular prion protein (PrPC) was identified in a genome-wide screen as a high-affinity receptor for Aβ oligomers, and since then, many studies have explored the role of PrPC in Alzheimer's disease. Herein, I systematically assess the current level of target validation for PrPC in Alzheimer's disease and the merits of the identified approaches to therapeutically affect the PrPC:Aβ oligomer-interaction. The interaction of Aβ oligomers with PrPC in mice impairs hippocampal long-term potentiation, memory, and learning in a manner that involves Fyn, tau, and glutamate receptors. Furthermore, PrPC acts to catalyze the formation of certain Aβ oligomeric species in the synapse and may mediate the toxic effects of other β-sheet rich oligomers as well. Therapeutic approaches utilizing soluble PrPC ectodomain or monoclonal antibodies targeting PrPC can at least partially prevent the neurotoxic effects of Aβ oligomers in mice. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/23948943/Cellular_prion_protein_as_a_therapeutic_target_in_Alzheimer's_disease_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-130950 DB - PRIME DP - Unbound Medicine ER -