Amyloid-β Induced Signaling by Cellular Prion Protein and Fyn Kinase in Alzheimer Disease

Overview

Journal Prion

Specialty Biochemistry

Date 2012 Sep 19

PMID 22987042

Citations 57

Authors

Ji Won Um

Stephen M Strittmatter

Affiliations

Soon will be listed here.

Abstract

Alzheimer disease (AD) is the most prevalent cause of dementia. Amyloid-β (Aβ) oligomers are potent synaptotoxins thought to mediate AD-related phenotypes. Cellular prion protein (PrP(C)) has been identified as a high-affinity receptor for Aβ oligomers. Herein, we review the functional consequences of Aβ oligomer binding to PrP(C) on the neuronal surface. We highlight recent evidence that Fyn kinase mediates signal transduction downstream of the PrP(C)-Aβ oligomer complex. These studies suggest that PrP(C) has a central role in AD pathogenesis and may provide a target for therapeutic intervention in AD.

Citing Articles

Cellular Prion Protein and Amyloid-β Oligomers in Alzheimer's Disease-Are There Connections?.

Fulek M, Hachiya N, Gachowska M, Beszlej J, Bartoszewska E, Kurpas D Int J Mol Sci. 2025; 26(5).

PMID: 40076721 PMC: 11900156. DOI: 10.3390/ijms26052097.

Single-Nucleus Landscape of Glial Cells and Neurons in Alzheimer's Disease.

Lu M, Li J, Huang Q, Mao D, Yang G, Lan Y Mol Neurobiol. 2024; 62(3):2695-2709.

PMID: 39153159 DOI: 10.1007/s12035-024-04428-6.

Fyn Kinase in Alzheimer's Disease: Unraveling Molecular Mechanisms and Therapeutic Implications.

Meur S, Karati D Mol Neurobiol. 2024; 62(1):643-660.

PMID: 38890236 DOI: 10.1007/s12035-024-04286-2.

primiReference: a reference for analysis of primary-microRNA expression in single-nucleus sequencing data.

Elias A, Nunez T, Kun B, Kreiling J J Genet Genomics. 2022; 50(2):108-121.

PMID: 36371075 PMC: 9974815. DOI: 10.1016/j.jgg.2022.10.003.

Alzheimer's disease/dementia-associated brain pathology in aging DPP6-KO mice.

Lin L, Petralia R, Holtzclaw L, Wang Y, Abebe D, Hoffman D Neurobiol Dis. 2022; 174:105887.

PMID: 36209950 PMC: 9617781. DOI: 10.1016/j.nbd.2022.105887.

References

Stuermer C, Langhorst M, Wiechers M, Legler D, Von Hanwehr S, Guse A . PrPc capping in T cells promotes its association with the lipid raft proteins reggie-1 and reggie-2 and leads to signal transduction. FASEB J. 2004; 18(14):1731-3. DOI: 10.1096/fj.04-2150fje. View

Resenberger U, Harmeier A, Woerner A, Goodman J, Muller V, Krishnan R . The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication. EMBO J. 2011; 30(10):2057-70. PMC: 3098494. DOI: 10.1038/emboj.2011.86. View

Lesne S, Koh M, Kotilinek L, Kayed R, Glabe C, Yang A . A specific amyloid-beta protein assembly in the brain impairs memory. Nature. 2006; 440(7082):352-7. DOI: 10.1038/nature04533. View

Bizat N, Peyrin J, Haik S, Cochois V, Beaudry P, Laplanche J . Neuron dysfunction is induced by prion protein with an insertional mutation via a Fyn kinase and reversed by sirtuin activation in Caenorhabditis elegans. J Neurosci. 2010; 30(15):5394-403. PMC: 6632766. DOI: 10.1523/JNEUROSCI.5831-09.2010. View

Lacor P, Buniel M, Furlow P, Clemente A, Velasco P, Wood M . Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J Neurosci. 2007; 27(4):796-807. PMC: 6672917. DOI: 10.1523/JNEUROSCI.3501-06.2007. View

Wu G, Hou X . Oligomerized Abeta25-35 induces increased tyrosine phosphorylation of NMDA receptor subunit 2A in rat hippocampal CA1 subfield. Brain Res. 2010; 1343:186-93. DOI: 10.1016/j.brainres.2010.04.055. View

Lambert M, Barlow A, Chromy B, Edwards C, Freed R, Liosatos M . Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci U S A. 1998; 95(11):6448-53. PMC: 27787. DOI: 10.1073/pnas.95.11.6448. View

Freir D, Nicoll A, Klyubin I, Panico S, Mc Donald J, Risse E . Interaction between prion protein and toxic amyloid β assemblies can be therapeutically targeted at multiple sites. Nat Commun. 2011; 2:336. PMC: 3156817. DOI: 10.1038/ncomms1341. View

Thomas S, Brugge J . Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol. 1997; 13:513-609. DOI: 10.1146/annurev.cellbio.13.1.513. View

10.

Hunter T . A tail of two src's: mutatis mutandis. Cell. 1987; 49(1):1-4. DOI: 10.1016/0092-8674(87)90745-8. View

11.

Chin J, Palop J, Puolivali J, Massaro C, Bien-Ly N, Gerstein H . Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer's disease. J Neurosci. 2005; 25(42):9694-703. PMC: 6725734. DOI: 10.1523/JNEUROSCI.2980-05.2005. View

12.

You H, Tsutsui S, Hameed S, Kannanayakal T, Chen L, Xia P . Aβ neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors. Proc Natl Acad Sci U S A. 2012; 109(5):1737-42. PMC: 3277185. DOI: 10.1073/pnas.1110789109. View

13.

Zou W, Xiao X, Yuan J, Puoti G, Fujioka H, Wang X . Amyloid-beta42 interacts mainly with insoluble prion protein in the Alzheimer brain. J Biol Chem. 2011; 286(17):15095-105. PMC: 3083157. DOI: 10.1074/jbc.M110.199356. View

14.

Benilova I, Karran E, De Strooper B . The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes. Nat Neurosci. 2012; 15(3):349-57. DOI: 10.1038/nn.3028. View

15.

Hardy J, Selkoe D . The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002; 297(5580):353-6. DOI: 10.1126/science.1072994. View

16.

Sinforiani E, Manni R, Bernasconi L, Banchieri L, Zucchella C . Memory disturbances and temporal lobe epilepsy simulating Alzheimer's disease: a case report. Funct Neurol. 2003; 18(1):39-41. View

17.

Um J, Nygaard H, Heiss J, Kostylev M, Stagi M, Vortmeyer A . Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nat Neurosci. 2012; 15(9):1227-35. PMC: 3431439. DOI: 10.1038/nn.3178. View

18.

Scheff S, DeKosky S, Price D . Quantitative assessment of cortical synaptic density in Alzheimer's disease. Neurobiol Aging. 1990; 11(1):29-37. DOI: 10.1016/0197-4580(90)90059-9. View

19.

Mi S, Lee X, Shao Z, Thill G, Ji B, Relton J . LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci. 2004; 7(3):221-8. DOI: 10.1038/nn1188. View

20.

Chung E, Ji Y, Sun Y, Kascsak R, Kascsak R, Mehta P . Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an Alzheimer's disease model mouse. BMC Neurosci. 2010; 11:130. PMC: 2964735. DOI: 10.1186/1471-2202-11-130. View