Open AccessThe O-Glycome of Human Nigrostriatal Tissue and Its Alteration in Parkinson’s Disease
Author(s) -
Hayden Wilkinson,
Kristina A. Thomsson,
Ana Lúcia Rebelo,
Mark Hilliard,
Abhay Pandit,
Pauline M. Rudd,
Niclas G. Karlsson,
Radka Saldova
Publication year - 2021
Publication title -
journal of proteome research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.644
H-Index - 161
eISSN - 1535-3907
pISSN - 1535-3893
DOI - 10.1021/acs.jproteome.1c00219
Subject(s) - glycome , substantia nigra , parkinson's disease , striatum , glycan , glycosylation , alpha synuclein , chemistry , biochemistry , disease , medicine , neuroscience , biology , dopamine , glycoprotein
O -Glycosylation changes in misfolded proteins are of particular interest in understanding neurodegenerative conditions such as Parkinson's disease (PD) and incidental Lewy body disease (ILBD). This work outlines optimizations of a microwave-assisted nonreductive release to limit glycan degradation and employs this methodology to analyze O -glycosylation on the human striatum and substantia nigra tissue in PD, ILBD, and healthy controls, working alongside well-established reductive release approaches. A total of 70 O -glycans were identified, with ILBD presenting significantly decreased levels of mannose-core ( p = 0.017) and glucuronylated structures ( p = 0.039) in the striatum and PD presenting an increase in sialylation ( p < 0.001) and a decrease in sulfation ( p = 0.001). Significant increases in sialylation ( p = 0.038) in PD were also observed in the substantia nigra. This is the first study to profile the whole nigrostriatal O -glycome in healthy, PD, and ILBD tissues, outlining disease biomarkers alongside benefits of employing orthogonal techniques for O -glycan analysis.