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Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta-mediated neurotoxicity

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Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta-mediated neurotoxicity. / Falker, Clemens; Hartmann, Alexander; Guett, Inga; Dohler, Frank; Altmeppen, Hermann; Betzel, Christian; Schubert, Robin; Thurm, Dana; Wegwitz, Florian; Joshi, Pooja; Verderio, Claudia; Krasemann, Susanne; Glatzel, Markus.

In: J NEUROCHEM, Vol. 137, No. 1, 01.04.2016, p. 88-100.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Falker, C, Hartmann, A, Guett, I, Dohler, F, Altmeppen, H, Betzel, C, Schubert, R, Thurm, D, Wegwitz, F, Joshi, P, Verderio, C, Krasemann, S & Glatzel, M 2016, 'Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta-mediated neurotoxicity', J NEUROCHEM, vol. 137, no. 1, pp. 88-100. https://doi.org/10.1111/jnc.13514

APA

Falker, C., Hartmann, A., Guett, I., Dohler, F., Altmeppen, H., Betzel, C., Schubert, R., Thurm, D., Wegwitz, F., Joshi, P., Verderio, C., Krasemann, S., & Glatzel, M. (2016). Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta-mediated neurotoxicity. J NEUROCHEM, 137(1), 88-100. https://doi.org/10.1111/jnc.13514

Vancouver

Falker C, Hartmann A, Guett I, Dohler F, Altmeppen H, Betzel C et al. Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta-mediated neurotoxicity. J NEUROCHEM. 2016 Apr 1;137(1):88-100. https://doi.org/10.1111/jnc.13514

Bibtex

@article{fefb7a2b78f64079866a10236ed29a4c,
title = "Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta-mediated neurotoxicity",
abstract = "Alzheimer's disease is a common neurodegenerative, progressive, and fatal disorder. Generation and deposition of amyloid beta (Aβ) peptides associate with its pathogenesis and small soluble Aβ oligomers show the most pronounced neurotoxic effects and correlate with disease initiation and progression. Recent findings showed that Aβ oligomers bind to the cellular prion protein (PrP(C) ) eliciting neurotoxic effects. The role of exosomes, small extracellular vesicles of endosomal origin, in Alzheimer's disease is only poorly understood. Besides serving as disease biomarkers they may promote Aβ plaque formation, decrease Aβ-mediated synaptotoxicity, and enhance Aβ clearance. Here we explore how exosomal PrP(C) connects to protective functions attributed to exosomes in Alzheimer's disease. To achieve this, we generated a mouse neuroblastoma PrP(C) knockout cell line using transcription activator-like effector nucleases. Using these, as well as SH-SY5Y human neuroblastoma cells, we show that PrP(C) is highly enriched on exosomes and that exosomes bind amyloid beta via PrP(C) . Exosomes showed highest binding affinity for dimeric, pentameric and oligomeric Aβ species. Thioflavin T assays revealed that exosomal PrP(C) accelerates fibrillization of amyloid beta, thereby reducing neurotoxic effects imparted by oligomeric Aβ. Our study provides further evidence for a protective role of exosomes in Aβ-mediated neurodegeneration and highlights the importance of exosomal PrP(C) in molecular mechanisms of Alzheimer's disease. This article is protected by copyright. All rights reserved.",
author = "Clemens Falker and Alexander Hartmann and Inga Guett and Frank Dohler and Hermann Altmeppen and Christian Betzel and Robin Schubert and Dana Thurm and Florian Wegwitz and Pooja Joshi and Claudia Verderio and Susanne Krasemann and Markus Glatzel",
note = "This article is protected by copyright. All rights reserved.",
year = "2016",
month = apr,
day = "1",
doi = "10.1111/jnc.13514",
language = "English",
volume = "137",
pages = "88--100",
journal = "J NEUROCHEM",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "1",

}

RIS

TY - JOUR

T1 - Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta-mediated neurotoxicity

AU - Falker, Clemens

AU - Hartmann, Alexander

AU - Guett, Inga

AU - Dohler, Frank

AU - Altmeppen, Hermann

AU - Betzel, Christian

AU - Schubert, Robin

AU - Thurm, Dana

AU - Wegwitz, Florian

AU - Joshi, Pooja

AU - Verderio, Claudia

AU - Krasemann, Susanne

AU - Glatzel, Markus

N1 - This article is protected by copyright. All rights reserved.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Alzheimer's disease is a common neurodegenerative, progressive, and fatal disorder. Generation and deposition of amyloid beta (Aβ) peptides associate with its pathogenesis and small soluble Aβ oligomers show the most pronounced neurotoxic effects and correlate with disease initiation and progression. Recent findings showed that Aβ oligomers bind to the cellular prion protein (PrP(C) ) eliciting neurotoxic effects. The role of exosomes, small extracellular vesicles of endosomal origin, in Alzheimer's disease is only poorly understood. Besides serving as disease biomarkers they may promote Aβ plaque formation, decrease Aβ-mediated synaptotoxicity, and enhance Aβ clearance. Here we explore how exosomal PrP(C) connects to protective functions attributed to exosomes in Alzheimer's disease. To achieve this, we generated a mouse neuroblastoma PrP(C) knockout cell line using transcription activator-like effector nucleases. Using these, as well as SH-SY5Y human neuroblastoma cells, we show that PrP(C) is highly enriched on exosomes and that exosomes bind amyloid beta via PrP(C) . Exosomes showed highest binding affinity for dimeric, pentameric and oligomeric Aβ species. Thioflavin T assays revealed that exosomal PrP(C) accelerates fibrillization of amyloid beta, thereby reducing neurotoxic effects imparted by oligomeric Aβ. Our study provides further evidence for a protective role of exosomes in Aβ-mediated neurodegeneration and highlights the importance of exosomal PrP(C) in molecular mechanisms of Alzheimer's disease. This article is protected by copyright. All rights reserved.

AB - Alzheimer's disease is a common neurodegenerative, progressive, and fatal disorder. Generation and deposition of amyloid beta (Aβ) peptides associate with its pathogenesis and small soluble Aβ oligomers show the most pronounced neurotoxic effects and correlate with disease initiation and progression. Recent findings showed that Aβ oligomers bind to the cellular prion protein (PrP(C) ) eliciting neurotoxic effects. The role of exosomes, small extracellular vesicles of endosomal origin, in Alzheimer's disease is only poorly understood. Besides serving as disease biomarkers they may promote Aβ plaque formation, decrease Aβ-mediated synaptotoxicity, and enhance Aβ clearance. Here we explore how exosomal PrP(C) connects to protective functions attributed to exosomes in Alzheimer's disease. To achieve this, we generated a mouse neuroblastoma PrP(C) knockout cell line using transcription activator-like effector nucleases. Using these, as well as SH-SY5Y human neuroblastoma cells, we show that PrP(C) is highly enriched on exosomes and that exosomes bind amyloid beta via PrP(C) . Exosomes showed highest binding affinity for dimeric, pentameric and oligomeric Aβ species. Thioflavin T assays revealed that exosomal PrP(C) accelerates fibrillization of amyloid beta, thereby reducing neurotoxic effects imparted by oligomeric Aβ. Our study provides further evidence for a protective role of exosomes in Aβ-mediated neurodegeneration and highlights the importance of exosomal PrP(C) in molecular mechanisms of Alzheimer's disease. This article is protected by copyright. All rights reserved.

U2 - 10.1111/jnc.13514

DO - 10.1111/jnc.13514

M3 - SCORING: Journal article

C2 - 26710111

VL - 137

SP - 88

EP - 100

JO - J NEUROCHEM

JF - J NEUROCHEM

SN - 0022-3042

IS - 1

ER -