Emerging roles of N-linked glycosylation in brain physiology and disorders

Lindsey R. Conroy; Tara R. Hawkinson; Lyndsay E.A. Young; Matthew S. Gentry; Ramon C. Sun

doi:10.1016/j.tem.2021.09.006

Emerging roles of N-linked glycosylation in brain physiology and disorders

Lindsey R. Conroy, Tara R. Hawkinson, Lyndsay E.A. Young, Matthew S. Gentry, Ramon C. Sun

Research output: Contribution to journal › Review article › peer-review

6 Scopus citations

Abstract

N-linked glycosylation is a complex, co- and post-translational series of events that connects metabolism to signaling in almost all cells. Metabolic assembly of N-linked glycans spans multiple cellular compartments, and early N-linked glycan biosynthesis is a central mediator of protein folding and the unfolded protein response (UPR). In the brain, N-linked glycosylated proteins participate in a myriad of processes, from electrical gradients to neurotransmission. However, it is less clear how perturbations in N-linked glycosylation impact and even potentially drive aspects of neurological disorders. In this review, we discuss our current understanding of the metabolic origins of N-linked glycans in the brain, their role in modulating neuronal function, and how aberrant N-linked glycosylation can drive neurological disorders.

Original language	English
Pages (from-to)	980-993
Number of pages	14
Journal	Trends in Endocrinology and Metabolism
Volume	32
Issue number	12
DOIs	https://doi.org/10.1016/j.tem.2021.09.006
State	Published - Dec 2021

Bibliographical note

Funding Information:
We would like to thank Vander Kooi and Charles J. Waechter, as well as members of the Gentry and Sun laboratories, for vigorous discussions regarding this work. This review was supported by National Institutes of Health (NIH) grants R01 AG066653 , St Baldrick’s Career Development Award, V-Scholar Grant, Rally Foundation Independent Investigator Grant to R.C.S., and R35 NS116824 and P01 NS097197 to M.S.G.; L.R.C. was supported by the NIH/NCI training grant T32CA165990 .

Funding Information:
We would like to thank Vander Kooi and Charles J. Waechter, as well as members of the Gentry and Sun laboratories, for vigorous discussions regarding this work. This review was supported by National Institutes of Health (NIH) grants R01 AG066653, St Baldrick's Career Development Award, V-Scholar Grant, Rally Foundation Independent Investigator Grant to R.C.S. and R35 NS116824 and P01 NS097197 to M.S.G.; L.R.C. was supported by the NIH/NCI training grant T32CA165990. R.C.S. and M.S.G. are consultants for Maze Therapeutics, M.S.G. is a consultant for Enable Therapeutics, Glut1-Deficiency Syndrome Foundation, and Chelsea's Hope. M.S.G. and R.C.S. are founders of Atterogen, LLC.

Publisher Copyright:
© 2021 Elsevier Ltd

Keywords

Alzheimer's disease
N-linked glycosylation
carbohydrate metabolism
neurodegeneration
neuroinflammation

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.tem.2021.09.006

Cite this

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title = "Emerging roles of N-linked glycosylation in brain physiology and disorders",

abstract = "N-linked glycosylation is a complex, co- and post-translational series of events that connects metabolism to signaling in almost all cells. Metabolic assembly of N-linked glycans spans multiple cellular compartments, and early N-linked glycan biosynthesis is a central mediator of protein folding and the unfolded protein response (UPR). In the brain, N-linked glycosylated proteins participate in a myriad of processes, from electrical gradients to neurotransmission. However, it is less clear how perturbations in N-linked glycosylation impact and even potentially drive aspects of neurological disorders. In this review, we discuss our current understanding of the metabolic origins of N-linked glycans in the brain, their role in modulating neuronal function, and how aberrant N-linked glycosylation can drive neurological disorders.",

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note = "Funding Information: We would like to thank Vander Kooi and Charles J. Waechter, as well as members of the Gentry and Sun laboratories, for vigorous discussions regarding this work. This review was supported by National Institutes of Health (NIH) grants R01 AG066653 , St Baldrick{\textquoteright}s Career Development Award, V-Scholar Grant, Rally Foundation Independent Investigator Grant to R.C.S., and R35 NS116824 and P01 NS097197 to M.S.G.; L.R.C. was supported by the NIH/NCI training grant T32CA165990 . Funding Information: We would like to thank Vander Kooi and Charles J. Waechter, as well as members of the Gentry and Sun laboratories, for vigorous discussions regarding this work. This review was supported by National Institutes of Health (NIH) grants R01 AG066653, St Baldrick's Career Development Award, V-Scholar Grant, Rally Foundation Independent Investigator Grant to R.C.S. and R35 NS116824 and P01 NS097197 to M.S.G.; L.R.C. was supported by the NIH/NCI training grant T32CA165990. R.C.S. and M.S.G. are consultants for Maze Therapeutics, M.S.G. is a consultant for Enable Therapeutics, Glut1-Deficiency Syndrome Foundation, and Chelsea's Hope. M.S.G. and R.C.S. are founders of Atterogen, LLC. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",

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AU - Conroy, Lindsey R.

AU - Hawkinson, Tara R.

AU - Young, Lyndsay E.A.

AU - Gentry, Matthew S.

AU - Sun, Ramon C.

N1 - Funding Information: We would like to thank Vander Kooi and Charles J. Waechter, as well as members of the Gentry and Sun laboratories, for vigorous discussions regarding this work. This review was supported by National Institutes of Health (NIH) grants R01 AG066653 , St Baldrick’s Career Development Award, V-Scholar Grant, Rally Foundation Independent Investigator Grant to R.C.S., and R35 NS116824 and P01 NS097197 to M.S.G.; L.R.C. was supported by the NIH/NCI training grant T32CA165990 . Funding Information: We would like to thank Vander Kooi and Charles J. Waechter, as well as members of the Gentry and Sun laboratories, for vigorous discussions regarding this work. This review was supported by National Institutes of Health (NIH) grants R01 AG066653, St Baldrick's Career Development Award, V-Scholar Grant, Rally Foundation Independent Investigator Grant to R.C.S. and R35 NS116824 and P01 NS097197 to M.S.G.; L.R.C. was supported by the NIH/NCI training grant T32CA165990. R.C.S. and M.S.G. are consultants for Maze Therapeutics, M.S.G. is a consultant for Enable Therapeutics, Glut1-Deficiency Syndrome Foundation, and Chelsea's Hope. M.S.G. and R.C.S. are founders of Atterogen, LLC. Publisher Copyright: © 2021 Elsevier Ltd

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N2 - N-linked glycosylation is a complex, co- and post-translational series of events that connects metabolism to signaling in almost all cells. Metabolic assembly of N-linked glycans spans multiple cellular compartments, and early N-linked glycan biosynthesis is a central mediator of protein folding and the unfolded protein response (UPR). In the brain, N-linked glycosylated proteins participate in a myriad of processes, from electrical gradients to neurotransmission. However, it is less clear how perturbations in N-linked glycosylation impact and even potentially drive aspects of neurological disorders. In this review, we discuss our current understanding of the metabolic origins of N-linked glycans in the brain, their role in modulating neuronal function, and how aberrant N-linked glycosylation can drive neurological disorders.

AB - N-linked glycosylation is a complex, co- and post-translational series of events that connects metabolism to signaling in almost all cells. Metabolic assembly of N-linked glycans spans multiple cellular compartments, and early N-linked glycan biosynthesis is a central mediator of protein folding and the unfolded protein response (UPR). In the brain, N-linked glycosylated proteins participate in a myriad of processes, from electrical gradients to neurotransmission. However, it is less clear how perturbations in N-linked glycosylation impact and even potentially drive aspects of neurological disorders. In this review, we discuss our current understanding of the metabolic origins of N-linked glycans in the brain, their role in modulating neuronal function, and how aberrant N-linked glycosylation can drive neurological disorders.

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KW - N-linked glycosylation

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KW - neurodegeneration

KW - neuroinflammation

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Emerging roles of N-linked glycosylation in brain physiology and disorders

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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