The O-Glycome of Human Nigrostriatal Tissue and Its Alteration in Parkinson’s Disease
| Autor: | Ana Lúcia Rebelo, Pauline M. Rudd, Radka Saldova, Kristina A. Thomsson, Hayden Wilkinson, Mark Hilliard, Niclas G. Karlsson, Abhay Pandit |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Lewy Body Disease medicine.medical_specialty Parkinson's disease striatum Substantia nigra liquid chromatography (LC) Striatum Biochemistry Article methods 03 medical and health sciences Sulfation O glycans Internal medicine exoglycosidases Medicine Disease biomarker Humans mass spectrometry (MS) O-glycans 030102 biochemistry & molecular biology business.industry biomarkers Neurodegenerative Diseases Parkinson Disease General Chemistry medicine.disease Parkinson’s disease (PD) Glycome Corpus Striatum carbohydrates (lipids) Substantia Nigra 030104 developmental biology Endocrinology business Lewy body disease β-elimination incidental Lewy bodies disease (ILBD) |
| Zdroj: | Journal of Proteome Research |
| ISSN: | 1535-3907 1535-3893 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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