ABSTRACT
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 Statement
The authors have declared no competing interest.
ABREVIATIONS
- ATF6
- activating transcription factor 6
- CNS
- Central nervous system
- DMB
- 1,2-diamino-4,5-methylenedioxybenzene Dihydrochloride
- ER
- Endoplasmic reticulum
- ERAD
- Endoplasmic reticulum associated protein degradation
- GFAP
- Glial fibrillary acidic protein
- GRP78
- heat shock protein 70, binding immunoglobulin protein (BiP)
- GRP94
- heat shock protein 90
- HBP
- Hexosamine biosynthetic pathway
- HILIC-UPLC
- Hydrophilic Interaction Liquid Chromatography - Ultra Performance Liquid Chromatography
- Iba1
- Ionized calcium binding adaptor molecule 1
- ILBD
- Incidental Lewy body disease
- IRE1
- Inositol requiring enzyme 1
- LC-MS
- Liquid chromatography-mass spectrometry
- LLO
- Lipid-linked oligosaccharide
- PERK
- Protein kinase-like endoplasmic reticulum kinase
- PAS
- periodic acid Schiff
- PD
- Parkinson’s disease
- PDI
- Protein disulphide isomerase
- UHPLC
- Ultra-High Performance Liquid Chromatography
- UGGT
- UDP-glucose:glycoprotein glucosyltransferase
- UPR
- Unfolded protein response
- VGIC
- voltage-gated ion channels
- WAX-UPLC
- Weak Anion Exchange - Ultra Performance Liquid Chromatography