PT  - JOURNAL ARTICLE
AU  - Ana Lúcia Rebelo
AU  - Richard R. Drake
AU  - Martina Marchetti-Deschmann
AU  - Radka Saldova
AU  - Abhay Pandit
TI  - Changes in Tissue Protein <em>N</em>-Glycosylation and Associated Molecular Signature Occur in the Human Parkinsonian Brain in a Region-Specific Manner
AID  - 10.1101/2022.05.19.492623
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.19.492623
4099  - http://biorxiv.org/content/early/2022/05/20/2022.05.19.492623.short
4100  - http://biorxiv.org/content/early/2022/05/20/2022.05.19.492623.full
AB  - Parkinson’s Disease (PD) associated state of neuroinflammation due to the aggregation of aberrant proteins is widely reported. One type of post-translational modification involved in protein stability is glycosylation. Here, we aimed to spatially characterise the human Parkinsonian nigro-striatal N-glycome, and related transcriptome/proteome, and its correlation with endoplasmic reticulum stress and unfolded protein response (UPR), providing a comprehensive characterisation of the PD molecular signature.Significant changes were seen upon PD: 3% increase in sialylation and 5% increase in fucosylation in both regions, and 2% increase in oligomannosylated N-glycans in the substantia nigra. In the latter, a decrease in the mRNA expression of sialidases and an upregulation in the UPR pathway were also seen.This complete characterisation of the human nigro-striatal N-glycome provides an insight into the glycomic profile of PD through a transversal approach while combining the other PD “omics” pieces, which can potentially assist in the development of glyco-focused therapeutics.Competing Interest StatementThe authors have declared no competing interest.ATF6activating transcription factor 6CNSCentral nervous systemDMB1,2-diamino-4,5-methylenedioxybenzene DihydrochlorideEREndoplasmic reticulumERADEndoplasmic reticulum associated protein degradationGFAPGlial fibrillary acidic proteinGRP78heat shock protein 70, binding immunoglobulin protein (BiP)GRP94heat shock protein 90HBPHexosamine biosynthetic pathwayHILIC-UPLCHydrophilic Interaction Liquid Chromatography - Ultra Performance Liquid ChromatographyIba1Ionized calcium binding adaptor molecule 1ILBDIncidental Lewy body diseaseIRE1Inositol requiring enzyme 1LC-MSLiquid chromatography-mass spectrometryLLOLipid-linked oligosaccharidePERKProtein kinase-like endoplasmic reticulum kinasePASperiodic acid SchiffPDParkinson’s diseasePDIProtein disulphide isomeraseUHPLCUltra-High Performance Liquid ChromatographyUGGTUDP-glucose:glycoprotein glucosyltransferaseUPRUnfolded protein responseVGICvoltage-gated ion channelsWAX-UPLCWeak Anion Exchange - Ultra Performance Liquid Chromatography