Summary
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 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. To show the correlation between these, we also describe an in vitro functional study where changes in specific glycosylation trait enzymes (inhibition of sialyltransferases) led to impairments in cell mitochondrial activity, changes in glyco-profile and upregulation in UPR pathways. 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.
Footnotes
Competing Interest Statement All authors declare they have no competing interests.
We have added fig 6 in the revised version. Which isIn vitro correlation study Influence of the downregulation of sialyltransferases in the cell metabolism, glycoprofile and ER stress. a. Schematic outline of the in vitro model, time points and concentrations of 3Fax-Peracetyl Neu5Ac used; b Mechanism of action of 3Fax-Peracetyl Neu5Ac it crosses the cell membrane and inhibits the attachment of sialic acid residues to glycan structures in the Golgi apparatus
