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Brain O-GlcNAcylation: From Molecular Mechanisms to Clinical Phenotype

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Glycobiology of the Nervous System

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 29))

Abstract

O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. It is generally not further elongated but exists as a monosaccharide that can be rapidly added or removed. Thousands of proteins involved in gene transcription, protein translation and degradation as well as the regulation of signal transduction contain O-GlcNAc. Brain is one of the tissues where O-GlcNAc is the most highly expressed and deletion of neuronal O-GlcNAc leads to death early in development. O-GlcNAc is also important for normal adult brain function, where dynamic processes like learning and memory at least in part depend on the modification of specific proteins by O-GlcNAc. Conversely, too much or too little O-GlcNAc in the brain contributes to several disorders including obesity, intellectual disability and Alzheimer’s disease. In this chapter, we describe the expression and regulation of O-GlcNAc in the nervous system.

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Abbreviations

aCamKII:

Alpha calcium/calmodulin-dependent protein kinase II

Agrp:

Agouti-related peptide

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic

APP:

Amyloid precursor protein

AP-2:

Adaptor protein complex 2

CNS:

Central nervous system

CREB:

Cyclic AMP-response element binding protein

CTD:

Carboxyl terminal domain

CTRC:

CREB-regulated transcription coactivator

Gtfs:

Glycosyltransferases

HBP:

Hexosamine biosynthesis pathway

ECD:

Electron capture dissociation

eIF2:

Eukaryotic initiation factor 2

ER:

Endoplasmatic reticulum

ETD:

Electron transfer dissociation

MAPK:

Mitogen-activated kinase

MeCP2:

Methyl CpG binding protein 2

mTOR:

Mammalian target of rapamycin

NSF:

N-ethylmaleimide-sensitive fusion protein

LTD:

Long-term depression

LTP:

Long-term potentiation

OGA:

O-GlcNAcase

O-GlcNAc:

O-linked N-acetylglucosamine

OGT:

O-GlcNAc transferase

P:

Phosphate

PET:

Positron emission tomography

PIP3:

Phosphatylinositol (3,4,5)-triphosphate

PPF:

Paired-pulse facilitation

PTM:

Post-translational modification

PVN:

Paraventricular nucleus of the hypothalamus

TPR:

Tetratricopeptide

UDP:

Uridine diphosphate

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Authors and Affiliations

  1. Unit for Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden

    Batuhan Uygar & Olof Lagerlöf

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  1. Batuhan Uygar
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  2. Olof Lagerlöf
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Correspondence to Olof Lagerlöf .

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  1. Biochemistry and Molecular Biology, The Pennsylvania State University, Hershey, PA, USA

    Cara-Lynne Schengrund

  2. Department of Neuroscience and Regenerative Medicine, Medical College of Georgia Augusta University, Augusta, GA, USA

    Robert K. Yu

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Uygar, B., Lagerlöf, O. (2023). Brain O-GlcNAcylation: From Molecular Mechanisms to Clinical Phenotype. In: Schengrund, CL., Yu, R.K. (eds) Glycobiology of the Nervous System. Advances in Neurobiology, vol 29. Springer, Cham. https://doi.org/10.1007/978-3-031-12390-0_9

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