Interplay between protein glycosylation pathways in Alzheimer’s disease

Moran Frenkel-Pinter; Merav Daniel Shmueli; Chen Raz; Michaela Yanku; Shai Zilberzwige; Ehud Gazit; Daniel Segal

doi:10.1126/sciadv.1601576

Interplay between protein glycosylation pathways in Alzheimer’s disease

Moran Frenkel-Pinter, Merav Daniel Shmueli, Chen Raz, Michaela Yanku, Shai Zilberzwige, Ehud Gazit, Daniel Segal^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

70 Scopus citations

Abstract

Deviations from the normal nucleoplasmic protein O-GlcNAcylation, as well as from normal protein sialylation and N-glycosylation in the secretory pathway, have been reported in Alzheimer’s disease (AD). However, the interplay between the cytoplasmic protein O-GlcNAcylation and the secretory N-/O-glycosylation in AD has not been described. We present a comprehensive analysis of the N-, O-, and O-GlcNAc–glycomes in AD-affected brain regions as well as in AD patient serum. We detected marked differences in levels of glycan involved in both protein O-GlcNAcylation and N-/O-glycosylation between patients and healthy individuals and revealed brain region–specific glycosylation-related pathology in patients. These alterations are not general for other neurodegenerative conditions, such as frontotemporal dementia and corticobasal degeneration. The alterations in the AD glycome in the serum could potentially lead to novel glyco-based biomarkers for AD progression. Strikingly, negative interrelationship was found between the pathways of protein O-GlcNAcylation and N-/O-glycosylation, suggesting a novel intracellular cross-talk.

Original language	American English
Article number	1601576
Journal	Science advances
Volume	3
Issue number	9
DOIs	https://doi.org/10.1126/sciadv.1601576
State	Published - 2017
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported in part by the Israel Science Foundation (#1130/13), the Israeli Ministry of Science and Technology, the Alliance Family Foundation, the Helmholtz Israel program, and the Rosetrees Trust (to D.S.). M.F.-P. gratefully acknowledges the Eshkol fellowship by the Israeli Ministry of Science and Technology. Tissue samples were supplied by The London Neurodegenerative Diseases Brain Bank at KCL, which receives funding from the Medical Research Council (MRC) and as part of the Brains for Dementia Research program, jointly funded by Alzheimer’s Research UK and Alzheimer’s Society.

Publisher Copyright:
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.

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abstract = "Deviations from the normal nucleoplasmic protein O-GlcNAcylation, as well as from normal protein sialylation and N-glycosylation in the secretory pathway, have been reported in Alzheimer{\textquoteright}s disease (AD). However, the interplay between the cytoplasmic protein O-GlcNAcylation and the secretory N-/O-glycosylation in AD has not been described. We present a comprehensive analysis of the N-, O-, and O-GlcNAc–glycomes in AD-affected brain regions as well as in AD patient serum. We detected marked differences in levels of glycan involved in both protein O-GlcNAcylation and N-/O-glycosylation between patients and healthy individuals and revealed brain region–specific glycosylation-related pathology in patients. These alterations are not general for other neurodegenerative conditions, such as frontotemporal dementia and corticobasal degeneration. The alterations in the AD glycome in the serum could potentially lead to novel glyco-based biomarkers for AD progression. Strikingly, negative interrelationship was found between the pathways of protein O-GlcNAcylation and N-/O-glycosylation, suggesting a novel intracellular cross-talk.",

author = "Moran Frenkel-Pinter and Shmueli, {Merav Daniel} and Chen Raz and Michaela Yanku and Shai Zilberzwige and Ehud Gazit and Daniel Segal",

note = "Funding Information: This work was supported in part by the Israel Science Foundation (#1130/13), the Israeli Ministry of Science and Technology, the Alliance Family Foundation, the Helmholtz Israel program, and the Rosetrees Trust (to D.S.). M.F.-P. gratefully acknowledges the Eshkol fellowship by the Israeli Ministry of Science and Technology. Tissue samples were supplied by The London Neurodegenerative Diseases Brain Bank at KCL, which receives funding from the Medical Research Council (MRC) and as part of the Brains for Dementia Research program, jointly funded by Alzheimer{\textquoteright}s Research UK and Alzheimer{\textquoteright}s Society. Publisher Copyright: Copyright {\textcopyright} 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.",

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AU - Gazit, Ehud

AU - Segal, Daniel

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N2 - Deviations from the normal nucleoplasmic protein O-GlcNAcylation, as well as from normal protein sialylation and N-glycosylation in the secretory pathway, have been reported in Alzheimer’s disease (AD). However, the interplay between the cytoplasmic protein O-GlcNAcylation and the secretory N-/O-glycosylation in AD has not been described. We present a comprehensive analysis of the N-, O-, and O-GlcNAc–glycomes in AD-affected brain regions as well as in AD patient serum. We detected marked differences in levels of glycan involved in both protein O-GlcNAcylation and N-/O-glycosylation between patients and healthy individuals and revealed brain region–specific glycosylation-related pathology in patients. These alterations are not general for other neurodegenerative conditions, such as frontotemporal dementia and corticobasal degeneration. The alterations in the AD glycome in the serum could potentially lead to novel glyco-based biomarkers for AD progression. Strikingly, negative interrelationship was found between the pathways of protein O-GlcNAcylation and N-/O-glycosylation, suggesting a novel intracellular cross-talk.

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Interplay between protein glycosylation pathways in Alzheimer’s disease

Abstract

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